EP1771458B9 - N-phenylphosphoric acid triamides, method for the production thereof and their use as agents for regulating or inhibiting enzymatic urea hydrolysis - Google Patents
N-phenylphosphoric acid triamides, method for the production thereof and their use as agents for regulating or inhibiting enzymatic urea hydrolysis Download PDFInfo
- Publication number
- EP1771458B9 EP1771458B9 EP05701353A EP05701353A EP1771458B9 EP 1771458 B9 EP1771458 B9 EP 1771458B9 EP 05701353 A EP05701353 A EP 05701353A EP 05701353 A EP05701353 A EP 05701353A EP 1771458 B9 EP1771458 B9 EP 1771458B9
- Authority
- EP
- European Patent Office
- Prior art keywords
- nitrophenyl
- urea
- phosphoric acid
- alkyl
- urease
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 title claims abstract description 142
- 239000004202 carbamide Substances 0.000 title claims abstract description 76
- 230000007062 hydrolysis Effects 0.000 title claims abstract description 20
- 238000006460 hydrolysis reaction Methods 0.000 title claims abstract description 20
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 11
- 238000000034 method Methods 0.000 title claims abstract description 10
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 4
- 230000002255 enzymatic effect Effects 0.000 title abstract description 5
- OMPVAQNHVHNJEC-UHFFFAOYSA-N n-diaminophosphorylaniline Chemical class NP(N)(=O)NC1=CC=CC=C1 OMPVAQNHVHNJEC-UHFFFAOYSA-N 0.000 title abstract description 5
- 239000003795 chemical substances by application Substances 0.000 title abstract description 3
- 230000001105 regulatory effect Effects 0.000 title abstract description 3
- -1 alkheteroaryl Chemical group 0.000 claims abstract description 73
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 14
- 239000001301 oxygen Substances 0.000 claims abstract description 14
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 12
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims abstract description 11
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 9
- 125000002877 alkyl aryl group Chemical group 0.000 claims abstract description 8
- 239000000460 chlorine Substances 0.000 claims abstract description 8
- 125000004404 heteroalkyl group Chemical group 0.000 claims abstract description 8
- 239000001257 hydrogen Substances 0.000 claims abstract description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 6
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 6
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 5
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims abstract description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000002252 acyl group Chemical group 0.000 claims abstract description 4
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 4
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 4
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims abstract description 4
- 125000003435 aroyl group Chemical group 0.000 claims abstract description 4
- 125000005333 aroyloxy group Chemical group 0.000 claims abstract description 4
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims abstract description 4
- 125000005110 aryl thio group Chemical group 0.000 claims abstract description 4
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 4
- 125000004366 heterocycloalkenyl group Chemical group 0.000 claims abstract description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 3
- 239000011737 fluorine Substances 0.000 claims abstract description 3
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 61
- 239000003337 fertilizer Substances 0.000 claims description 47
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 43
- 150000001875 compounds Chemical class 0.000 claims description 29
- 229910021529 ammonia Inorganic materials 0.000 claims description 28
- 239000000203 mixture Substances 0.000 claims description 27
- 241001465754 Metazoa Species 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- GDPVISFVPDYFPN-UHFFFAOYSA-N n-[amino(hydroxy)phosphinimyl]-2-nitroaniline Chemical class NP(N)(=O)NC1=CC=CC=C1[N+]([O-])=O GDPVISFVPDYFPN-UHFFFAOYSA-N 0.000 claims description 20
- 108010046334 Urease Proteins 0.000 claims description 16
- 239000003112 inhibitor Substances 0.000 claims description 14
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 210000003608 fece Anatomy 0.000 claims description 10
- 230000005764 inhibitory process Effects 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 239000010871 livestock manure Substances 0.000 claims description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- DPJCXCZTLWNFOH-UHFFFAOYSA-N 2-nitroaniline Chemical class NC1=CC=CC=C1[N+]([O-])=O DPJCXCZTLWNFOH-UHFFFAOYSA-N 0.000 claims description 7
- 125000003282 alkyl amino group Chemical group 0.000 claims description 7
- QGBSISYHAICWAH-UHFFFAOYSA-N dicyandiamide Chemical compound NC(N)=NC#N QGBSISYHAICWAH-UHFFFAOYSA-N 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 5
- 150000002926 oxygen Chemical class 0.000 claims description 5
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical class C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 239000012298 atmosphere Substances 0.000 claims description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 208000007386 hepatic encephalopathy Diseases 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 150000003217 pyrazoles Chemical class 0.000 claims description 4
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 3
- 206010017964 Gastrointestinal infection Diseases 0.000 claims description 3
- DEGNHSNNGMQUPG-UHFFFAOYSA-N [O-][N+](C1=CC=CC=C1NP(O)(O)=O)=O.Cl.Cl Chemical class [O-][N+](C1=CC=CC=C1NP(O)(O)=O)=O.Cl.Cl DEGNHSNNGMQUPG-UHFFFAOYSA-N 0.000 claims description 3
- 239000013543 active substance Substances 0.000 claims description 3
- 125000004450 alkenylene group Chemical group 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 235000019253 formic acid Nutrition 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 3
- 238000002955 isolation Methods 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000011707 mineral Substances 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 231100000331 toxic Toxicity 0.000 claims description 3
- 230000002588 toxic effect Effects 0.000 claims description 3
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 claims description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- 208000014644 Brain disease Diseases 0.000 claims description 2
- 206010007027 Calculus urinary Diseases 0.000 claims description 2
- 206010010075 Coma hepatic Diseases 0.000 claims description 2
- 208000032274 Encephalopathy Diseases 0.000 claims description 2
- 239000004606 Fillers/Extenders Substances 0.000 claims description 2
- 241000590002 Helicobacter pylori Species 0.000 claims description 2
- 206010029148 Nephrolithiasis Diseases 0.000 claims description 2
- 206010037596 Pyelonephritis Diseases 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 235000013305 food Nutrition 0.000 claims description 2
- 230000002496 gastric effect Effects 0.000 claims description 2
- 229940037467 helicobacter pylori Drugs 0.000 claims description 2
- 201000001059 hepatic coma Diseases 0.000 claims description 2
- 150000003840 hydrochlorides Chemical class 0.000 claims description 2
- 230000002757 inflammatory effect Effects 0.000 claims description 2
- 208000028774 intestinal disease Diseases 0.000 claims description 2
- 239000012669 liquid formulation Substances 0.000 claims description 2
- 238000011321 prophylaxis Methods 0.000 claims description 2
- 208000018556 stomach disease Diseases 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- 208000008281 urolithiasis Diseases 0.000 claims description 2
- 239000005864 Sulphur Chemical group 0.000 claims 3
- 239000011261 inert gas Substances 0.000 claims 2
- MJFDUWNEHPLBPH-UHFFFAOYSA-N (2-nitroanilino)phosphonic acid hydrochloride Chemical class Cl.OP(O)(=O)NC1=CC=CC=C1[N+]([O-])=O MJFDUWNEHPLBPH-UHFFFAOYSA-N 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
- 229910019213 POCl3 Inorganic materials 0.000 claims 1
- 230000033228 biological regulation Effects 0.000 claims 1
- 238000011109 contamination Methods 0.000 claims 1
- 208000019836 digestive system infectious disease Diseases 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 208000015181 infectious disease Diseases 0.000 claims 1
- 239000012749 thinning agent Substances 0.000 claims 1
- 238000011144 upstream manufacturing Methods 0.000 claims 1
- 230000002485 urinary effect Effects 0.000 claims 1
- 229910052717 sulfur Chemical group 0.000 abstract description 7
- 239000011593 sulfur Chemical group 0.000 abstract description 5
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 abstract description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 3
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 abstract description 2
- 125000004093 cyano group Chemical group *C#N 0.000 abstract description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 abstract 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 1
- 235000013877 carbamide Nutrition 0.000 description 66
- 239000002601 urease inhibitor Substances 0.000 description 22
- 239000002689 soil Substances 0.000 description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 239000000243 solution Substances 0.000 description 9
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- HEPPIYNOUFWEPP-UHFFFAOYSA-N n-diaminophosphinothioylbutan-1-amine Chemical compound CCCCNP(N)(N)=S HEPPIYNOUFWEPP-UHFFFAOYSA-N 0.000 description 8
- 241000282849 Ruminantia Species 0.000 description 7
- 150000003254 radicals Chemical group 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 230000004720 fertilization Effects 0.000 description 6
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical group O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 125000000304 alkynyl group Chemical group 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 125000003342 alkenyl group Chemical group 0.000 description 4
- 235000019270 ammonium chloride Nutrition 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 229940090496 Urease inhibitor Drugs 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 125000002837 carbocyclic group Chemical group 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 235000015097 nutrients Nutrition 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 239000011574 phosphorus Substances 0.000 description 3
- 230000001863 plant nutrition Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 210000004767 rumen Anatomy 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 0 CC*(C)C1CC(CC(C)=C)CC1 Chemical compound CC*(C)C1CC(CC(C)=C)CC1 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- DMSZORWOGDLWGN-UHFFFAOYSA-N ctk1a3526 Chemical class NP(N)(N)=O DMSZORWOGDLWGN-UHFFFAOYSA-N 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 125000001072 heteroaryl group Chemical group 0.000 description 2
- 230000002262 irrigation Effects 0.000 description 2
- 238000003973 irrigation Methods 0.000 description 2
- 238000002386 leaching Methods 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- VAQQGIYBOFOIAH-UHFFFAOYSA-N n-diaminophosphoryl-3-methylaniline Chemical compound CC1=CC=CC(NP(N)(N)=O)=C1 VAQQGIYBOFOIAH-UHFFFAOYSA-N 0.000 description 2
- OPCLSODPVPLTGH-UHFFFAOYSA-N n-diaminophosphoryl-4-methyl-2-nitroaniline Chemical compound CC1=CC=C(NP(N)(N)=O)C([N+]([O-])=O)=C1 OPCLSODPVPLTGH-UHFFFAOYSA-N 0.000 description 2
- 239000000618 nitrogen fertilizer Substances 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 230000035764 nutrition Effects 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 238000005987 sulfurization reaction Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 description 2
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 1
- YGTAZGSLCXNBQL-UHFFFAOYSA-N 1,2,4-thiadiazole Chemical compound C=1N=CSN=1 YGTAZGSLCXNBQL-UHFFFAOYSA-N 0.000 description 1
- FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 description 1
- UDGKZGLPXCRRAM-UHFFFAOYSA-N 1,2,5-thiadiazole Chemical compound C=1C=NSN=1 UDGKZGLPXCRRAM-UHFFFAOYSA-N 0.000 description 1
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 1
- MBIZXFATKUQOOA-UHFFFAOYSA-N 1,3,4-thiadiazole Chemical compound C1=NN=CS1 MBIZXFATKUQOOA-UHFFFAOYSA-N 0.000 description 1
- JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical compound C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 description 1
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
- SPJXGIDHWJCRSL-UHFFFAOYSA-N 2-[[4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound CSCCC(C(O)=O)NC(=O)C(CC(C)C)NC(=O)OC(C)(C)C SPJXGIDHWJCRSL-UHFFFAOYSA-N 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- KVHLHAXJDWEQAB-UHFFFAOYSA-N 4-methyl-2-nitroaniline;hydrochloride Chemical compound Cl.CC1=CC=C(N)C([N+]([O-])=O)=C1 KVHLHAXJDWEQAB-UHFFFAOYSA-N 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- SBUKLPSBNFWJCU-UHFFFAOYSA-N ClIBr Chemical compound ClIBr SBUKLPSBNFWJCU-UHFFFAOYSA-N 0.000 description 1
- 108010082495 Dietary Plant Proteins Proteins 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical class O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 235000019728 animal nutrition Nutrition 0.000 description 1
- 239000010828 animal waste Substances 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- PPBAJDRXASKAGH-UHFFFAOYSA-N azane;urea Chemical compound N.NC(N)=O PPBAJDRXASKAGH-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000000035 biogenic effect Effects 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000004495 emulsifiable concentrate Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- JKFAIQOWCVVSKC-UHFFFAOYSA-N furazan Chemical compound C=1C=NON=1 JKFAIQOWCVVSKC-UHFFFAOYSA-N 0.000 description 1
- 230000035784 germination Effects 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000004474 heteroalkylene group Chemical group 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
- 230000035987 intoxication Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000003621 irrigation water Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- JIQNWFBLYKVZFY-UHFFFAOYSA-N methoxycyclohexatriene Chemical compound COC1=C[C]=CC=C1 JIQNWFBLYKVZFY-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 125000004370 n-butenyl group Chemical group [H]\C([H])=C(/[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910017464 nitrogen compound Inorganic materials 0.000 description 1
- 239000003895 organic fertilizer Substances 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical group C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000004546 suspension concentrate Substances 0.000 description 1
- 229940042055 systemic antimycotics triazole derivative Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- WQYSXVGEZYESBR-UHFFFAOYSA-N thiophosphoryl chloride Chemical compound ClP(Cl)(Cl)=S WQYSXVGEZYESBR-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/22—Amides of acids of phosphorus
- C07F9/224—Phosphorus triamides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/04—Drugs for disorders of the urinary system for urolithiasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C05—FERTILISERS; MANUFACTURE THEREOF
- C05B—PHOSPHATIC FERTILISERS
- C05B15/00—Organic phosphatic fertilisers
-
- C—CHEMISTRY; METALLURGY
- C05—FERTILISERS; MANUFACTURE THEREOF
- C05G—MIXTURES OF FERTILISERS COVERED INDIVIDUALLY BY DIFFERENT SUBCLASSES OF CLASS C05; MIXTURES OF ONE OR MORE FERTILISERS WITH MATERIALS NOT HAVING A SPECIFIC FERTILISING ACTIVITY, e.g. PESTICIDES, SOIL-CONDITIONERS, WETTING AGENTS; FERTILISERS CHARACTERISED BY THEIR FORM
- C05G3/00—Mixtures of one or more fertilisers with additives not having a specially fertilising activity
- C05G3/90—Mixtures of one or more fertilisers with additives not having a specially fertilising activity for affecting the nitrification of ammonium compounds or urea in the soil
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P60/00—Technologies relating to agriculture, livestock or agroalimentary industries
- Y02P60/20—Reduction of greenhouse gas [GHG] emissions in agriculture, e.g. CO2
- Y02P60/21—Dinitrogen oxide [N2O], e.g. using aquaponics, hydroponics or efficiency measures
Definitions
- the present invention relates to novel N - (2-nitrophenyl) phosphoric, processes for their preparation, compositions containing them and use of these N - (2-nitrophenyl) phosphoric or compositions containing them (urease) as a means for regulating or inhibiting the enzymatic Urea hydrolysis (also in combination with nitrification inhibitors) to avoid nitrogen losses in the application of urea-based fertilizers and to reduce the ammonia load in animal sheds due to the elimination of urea hydrolysis and as an additive to feed urea as part of animal nutrition, especially of ruminants.
- the invention further relates to fertilizer compositions containing N- phenylphosphoric triamides and a urea-based fertilizer.
- Urea is an originally biogenic metabolite, which is split by the enzyme urease into ammonia and carbon dioxide.
- the reaction is extremely rapid and effective, and is therefore responsible for N losses in the application of urea-based fertilizers. These are particularly high if the soil does not have sufficient sorption power to bind the liberated ammonia in the form of ammonium ions.
- agriculture loses considerable amounts of nitrogen every year, contributing to environmental pollution and requiring increased fertilizer requirements.
- urea is the largest N-containing nitrogen fertilizer and the world's most abundant N fertilizer
- the search for workable solutions to reduce urease-induced N losses becomes understandable.
- a variety of solutions have been proposed.
- the acid coating of urea prills or granules in order to be able to absorb ammonia formed by salt formation, or the coating with substances, whereby urea is released slowed down and thus the resulting ammonia can be easily »buffered «.
- N losses from the urease-catalyzed hydrolysis of urea and nitrification may be up to 50% under unfavorable conditions, especially in tropical and subtropical climates.
- multi-split fertilizer feeds are recommended as needed, which, however, entail significant labor-management disadvantages and corresponding additional expenses for the farmer as a result of additional application costs.
- Options for limiting nitrogen losses include the targeted inhibition of urease-catalyzed urea hydrolysis on the one hand and nitrification inhibition on the other.
- the use of such substances appears promising, which lead to urease inhibition, which in addition to the application for fertilization purposes, of course, the application for minimizing the ammonia load in animal sheds or their addition to feed urea offers.
- urease inhibitors are an effective way to significantly slow down the enzymatic urea hydrolysis, which is extremely rapid under normal conditions. Due to the delay of this enzyme reaction, the fertilizer urea can penetrate undecomposed into deeper soil layers.
- NPN compounds non-protein-nitrogen compounds
- the urea can take on this role if it is possible to control the urease-catalyzed urea hydrolysis taking place in the rumen of the animals in such a way that the released ammonia rates are immediately processed into microbial protein by the presence of microorganisms and consequently can not trigger any toxic effects.
- suitable urease inhibitors is also suitable here.
- phosphoric acid ester diamides ( DD 122 177 ) compounds have been found which are extremely effective urease inhibitors.
- phosphoric triamide including the main body (cf., for example, US Pat. US 4,540,428 . US 4,676,822 . US 4,696,693 . US 4,537,614 . US 4,517,004 . EP 0 119 487 ), of which the N- (n-butyl) thiophosphoric triamide (NBTPT) has been commercialized as the sole representative (IMC AGRICO Corp., product name Agrotain®).
- NBTPT N- (n-butyl) thiophosphoric triamide
- NBTPT fails under anaerobic conditions in rice cultivation, ie precisely where the highest nitrogen losses and ammonia emissions are recorded, since the formation of the oxygen analogue of NBTPT and thus of the actual urease inhibitor is not or only slowly possible (cf. Fertilizer Research 42, 251 (1995 )).
- N losses due to uncontrolled urease-catalyzed hydrolysis of urea nitrogen is lost in the form of nitrate, which is removed by leaching or transfer to deeper soil layers of plant nutrition.
- these N losses can be increased even if in the course of the rapid nitrification of ammonium ions relatively large amounts of nitrate are formed, which in turn can be converted by incipient denitrification in molecular nitrogen and thus are also no longer available for plant nutrition.
- nitrification inhibitors for example, substituted pyrazoles ( DD 131 063 . US 3,635,690 ), Triazoles ( DE-OS 18 04 994 . US 3,697,244 . US 3,701,645 ) but also drug combinations based on pyrazole compounds and dicyandiamide ( DD 227 957 ) or of triazole derivatives and dicyandiamide ( WO 95/22 515 ) has been proposed.
- NBTPT N- (n-butyl) thiophosphoric triamide
- DCD dicyandiamide
- US-A-4,242,325 discloses certain phosphoric triamides as urease inhibitors. Among others, a 4-nitrophenyl derivative is indicated.
- the present invention therefore an object of the invention to provide such urease inhibitors for the practice available when used with fertilizer or other urea-based fertilizers are able to limit the enzyme-catalyzed urea hydrolysis to such an extent that the resulting nitrogen losses in the form of ammonia are almost impossible or the ammonia load in animal houses by spontaneous decomposition of urea is significantly reduced.
- the new urease inhibitors should be combinable with nitrification inhibitors without any loss of effect in order to achieve a further improvement in N utilization in urea-based fertilizers.
- these urease inhibitors should slow down the urea cleavage in the rumen of ruminants when using urea as part of animal feeding so that the animals suffer no damage from otherwise taking ammonia intoxications and on the other hand can utilize the thus offered nitrogen for the body's protein biosynthesis.
- the urease inhibitors can be used for the prophylaxis or therapy of disorders or diseases that are induced or promoted directly or indirectly by urease activity. Examples include catheter encrustation, inflammatory and ulcerative gastric and intestinal diseases, urolithiasis, pyelonephritis, nephrolithiasis, ammonia encephalopathy, hepatic encephalopathy, hepatic coma, urinary tract infections, and gastrointestinal infections. These can be caused for example by urease-producing microorganisms such as Helicobacter pylori.
- N - (2-nitrophenyl) phosphoric triamides provided and used according to the invention, with suitable substitution on the phenyl radical, are highly effective urease inhibitors with an extremely long-lasting effect.
- - (2-nitrophenyl) phosphoric also technical problems and cost-effectively from simple starting materials.
- the N inventive - (2-nitrophenyl) phosphoric come equipped with common Method easily incorporated into urea or urea-based fertilizers, which is an efficient application together with the fertilizer or feeding to ruminants possible. They are both sufficiently water-soluble and well oil-soluble, which was also unpredictable.
- Another advantage of the invention N - (2-nitrophenyl) phosphoric whose easy combinability with nitrification inhibitors.
- the invention further relates to methods for the preparation of N invention - (2-nitrophenyl) phosphoric acid triamides as defined in claim 3, compositions containing these n - (2-nitrophenyl) phosphoric acid triamides as defined in claim 3, a fertilizer composition as defined in claim 7 and the uses defined in claims 10 to 16.
- radicals R 1 -R 4 may optionally be substituted independently and independently of one another by one or more of the abovementioned groups and by amino, alkylamino, dialkylamino, hydroxy, mercapto.
- Two adjacent radicals R (for example R 1 and R 2 ) may be linked to one another via an alkylene or alkenylene chain to form a 5-6-membered, optionally aromatic ring system which may contain one or more heteroatoms, such as oxygen, Contain nitrogen or sulfur and may be substituted by the above groups.
- a preferred N- (2-nitrophenyl) phosphoric triamide of the present invention corresponds to the formula (II):
- the invention includes salts, tautomers and metal complexes of compounds of the general formula (I) or (II) which have urease-inhibiting activity.
- alkyl, alkenyl or alkynyl groups with the corresponding carbon number mentioned below may be straight-chain or branched and mono- or polyunsaturated.
- alkyl group "heteroalkyl group” or “cycloalkyl group”, etc. is used occasionally for the sake of simplicity, to avoid unnecessary redundancy, the corresponding unsaturated groups should be included in each case. It will be understood by those skilled in the art that alkenyl or alkynyl groups must have at least 2 carbon atoms and cyclic hydrocarbon groups must have at least 3 carbon atoms.
- alkyl refers to any combination with any other groups, especially an alkyl group having from 1 to 8 carbon atoms, e.g. a methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, amyl, isoamyl, n-hexyl, 2,2-dimethylbutyl or n-octyl group.
- alkenyl refers to any combination with any other groups, especially an alkenyl group having from 2 to 8 carbon atoms, e.g. an ethenyl, n-propenyl, isopropenyl, n-butenyl, isobutenyl, tert-butenyl, n-hexenyl, 2,2-dimethylbutenyl, n-octenyl, allyl, isoprenyl or hex-2 enyl group.
- an alkenyl group having from 2 to 8 carbon atoms e.g. an ethenyl, n-propenyl, isopropenyl, n-butenyl, isobutenyl, tert-butenyl, n-hexenyl, 2,2-dimethylbutenyl, n-octenyl, allyl, isoprenyl or hex-2 enyl group.
- alkynyl refers to any combination with any other groups, especially an alkynyl group having from 2 to 8 carbon atoms, e.g. an ethynyl, n-propynyl, isopropynyl, n-butynyl, isobutinyl, tert-butynyl, n-hexynyl, 2,2-dimethylbutynyl or n-octynyl group.
- heteroalkyl refers with respect to the alkyl part to an alkyl group as defined above, but should also include a corresponding heteroalkenyl or heteroalkynyl group in which one or more carbon atoms by at least one oxygen, nitrogen, phosphorus or Sulfur atom are replaced.
- aryl refers to an aromatic cyclic group having one or more rings and is formed by a skeleton containing 6 to 10 ring carbon atoms. Of course, in the case of several rings, one or more rings may be completely or partially hydrogenated (an example being the 1,2,3,4-tetrahydro-naphthalen-1-yl group).
- an aryl group may be substituted by alkyl or heteroalkyl groups (each as defined above). Examples are a phenyl, naphthyl, indene, 2-, 3- or 4-methoxyphenyl, 2-, 3- or 4-ethoxyphenyl, 4-carboxyphenylalkyl or 4-hydroxyphenyl group.
- aralkyl or “heteroarylalkyl” refer to groups which according to the above or following definitions are both aryl or heteroaryl (defined below) as well as alkyl and / or heteroalkyl (also the corresponding alkylene / Heteroalkylene and alkynyl / heteroalkynyl groups) and / or carbocyclic groups (defined below) and / or heterocycloalkyl ring systems (defined below), eg a tetrahydroisoquinolinyl, benzyl, 2- or 3-ethyl-indolyl or 4-methylpyridino group.
- aralkyl and “heteroarylalkyl” are also intended to include the terms “alkaryl” and “alkheteroaryl” to avoid unnecessary redundancy.
- cycloalkyl or “carbocyclic” refers to a saturated or partially unsaturated, cyclic, optionally branched, group having one or more rings forming a skeleton containing from 3 to 8 carbon atoms, e.g. a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetralin, cyclopentenyl or cyclohex-2-enyl group.
- heterocycloalkyl refers to the above-defined cycloalkyl or carbocyclic groups in which one or more carbon atoms are replaced by one or more oxygen, nitrogen, phosphorus or sulfur atoms. Specific examples are aziridine, furan, pyrrolidine, piperidine, morpholine, oxazolidine, thiazolidine, N-methylpiperazino or N-phenylpiperazine groups.
- heteroaryl refers to an aryl group of 5 to 10 ring atoms in which one or more carbon atoms are replaced by an oxygen, nitrogen, phosphorus or sulfur atom.
- examples are pyrrole, furan, thiophene, pyrazole, isoxazole, isothiazole, imidazole, oxazole, thiazole, 1,2,4-triazole, 1,2,4-oxadiazole, 1,2 , 4-thiadiazole, 1,3,4-oxadiazole, 1,3,4-thiadiazole, 1,2,5-oxadiazole, 1,2,5-thiadiazole, tetrazole, pyridine, pyridazine, pyrimidine , Pyrazine, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine and indole groups.
- the N invention - (2-nitrophenyl) phosphoric or compositions containing the same have with appropriate substitution on the phenyl radical excellent for practical purposes inhibitory effect on, whereby they can slow down or the enzymatic urea hydrolysis so temporarily turn that ammonia losses under fertilizer treatments using organic and / or mineral urea-containing nitrogen fertilizer are reduced to a minimum or the occurrence of harmful or troublesome ammonia concentrations in animal husbandry is excluded, for example by urea degradation in animal excreta or by the degradation of feed urea in the rumen as part of the ruminant diet.
- N inventive - (2-nitrophenyl) phosphoric or compositions containing them extends or fertilizer treatments or preventive measures to avoid high concentrations of ammonia in livestock barns but is used for the use of feed urea within the framework of ruminant nutrition.
- the compounds according to the invention are preferably applied together with urea-based fertilizers, preferably in an amount of 0.001 to 10% by weight, based on the weight of the urea-based fertilizer, or added to the feed urea or animal waste arising in animal stalls. It is immaterial, for example, in the context of fertilization measures, whether they are superficially previously applied to the fertilizer, incorporated therein or applied together or in a reasonable time separately from urea-containing fertilizers.
- compositions containing the inventively used N - (2-nitrophenyl) phosphoric triamides and a urea-based mineral and / or organic fertilizer are thus compositions containing the inventively used N - (2-nitrophenyl) phosphoric triamides and a urea-based mineral and / or organic fertilizer.
- the compounds suitable according to the invention can be used in various ways and applied or applied.
- the compounds of the invention may be incorporated into the urea or urea-containing fertilizers prior to or during granulation from the molten phase. Furthermore, they can be applied to the surface of the urea or fertilizer granules or added to liquid urea-containing fertilizers. Finally, it is possible to add the urease inhibitors to organic urea-containing fertilizers, such as manure or manure. In addition, the compounds according to the invention can also be applied separately in the field in addition to the application of urea-based fertilizers in a preceding or subsequent work step.
- the compounds according to the invention can be used in pure form as pulverfömiger substance, granules or melt, aqueous solution or as a special formulation, mixed with the usual and known in the art auxiliaries, carriers and extenders or a combination of these agents. It is irrelevant whether the active ingredient in liquid form as z.
- Wettable powders, emulsifiable concentrates and suspension concentrates usually, but not necessarily, contain surfactants, e.g. As a wetting, dispersing, emulsifying or suspending agent.
- surfactants e.g. As a wetting, dispersing, emulsifying or suspending agent.
- the respective formulation methods correspond to the prior art and are known to the person skilled in the art.
- the compounds, compositions and fertilizers according to the invention can be used, for example, in and for fertigation.
- fertigation is meant the targeted supply of nutrients with the irrigation water, which can be applied eg by drip irrigation, spraying or sprinkling.
- the plants receive only the amount of water required for optimal growth so that no excess water is produced. Lack of vertical water movement in the soil beneath the rooting zone virtually eliminates nutrient leaching losses.
- Drip irrigation, spraying or sprinkling with urease inhibitors can be done, for example, after fertilization or together with the fertilizer.
- aqueous solutions or other formulations for example, sprayable suspensions of fine particles can also be used. Insofar let's be an example EP 1 378 499 and WO2004 / 013253 directed.
- the remaining oil is taken up without further purification in 50 ml of chloroform and added dropwise with exclusion of moisture at -50 to -30 ° C with stirring to a solution of about 30 ml of liquid ammonia in 50 ml of chloroform. Subsequently, the excess ammonia is allowed to evaporate overnight at room temperature.
- the ammonium chloride-containing crude product is filtered off with suction and, to remove the ammonium chloride, either boiled with diethylamine in chloroform or washed with a little water.
- ammonium chloride-containing crude product is filtered off with suction and, to remove the ammonium chloride, either boiled with diethylamine in chloroform or washed with a little water. This gives 9.1 g (49%) of N - (3-methylphenyl) phosphoric triamide.
- the percentage inhibition of the urea hydrolysis is calculated as a function of time or calculated from these values of the t 50 value.
- the t 50 value is the time in days after the start of the experiment at which the inhibition of urea hydrolysis is still 50%.
- Table 1 gives an overview of the inhibition data of some selected compounds of the invention determined by this method.
- Table 1 Urease inhibition (t ⁇ sub> 50 ⁇ / sub> value) after days by ⁇ i> N - ⁇ / i> phenylphosphoric triamides of the general formula (I) Connection no. Conc. A) % HS-N-mar.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Urology & Nephrology (AREA)
- Neurosurgery (AREA)
- Pest Control & Pesticides (AREA)
- Soil Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Gastroenterology & Hepatology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Toxicology (AREA)
- Fertilizers (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Fodder In General (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Die vorliegende Erfindung betrifft neue N-(2-Nitrophenyl)phosphorsäuretriamide, Verfahren zu ihrer Herstellung, diese enthaltende Zusammensetzungen und die Verwendung dieser N-(2-Nitrophenyl)phosphorsäuretriamide oder diese enthaltenden Zusammensetzungen als Mittel zur Regulierung bzw. Hemmung der enzymatischen (ureasekatalysierten) Harnstoff-Hydrolyse (auch in Kombination mit Mitteln zur Einschränkung der Nitrifikation) zur Vermeidung von Stickstoffverlusten bei der Anwendung harnstoffbasierter Düngemittel, sowie zur Reduzierung der Ammoniakbelastung in Tierställen infolge einer weitestgehenden Ausschaltung der Harnstoff-Hydrolyse und als Zusatz zu Futterharnstoff im Rahmen der Tierernährung, speziell von Wiederkäuern. Die Erfindung betrifft weiterhin Düngemittelzusammensetzungen, welche N-Phenylphosphorsäuretriamide und ein harnstoffbasiertes Düngemittel enthalten.The present invention relates to novel N - (2-nitrophenyl) phosphoric, processes for their preparation, compositions containing them and use of these N - (2-nitrophenyl) phosphoric or compositions containing them (urease) as a means for regulating or inhibiting the enzymatic Urea hydrolysis (also in combination with nitrification inhibitors) to avoid nitrogen losses in the application of urea-based fertilizers and to reduce the ammonia load in animal sheds due to the elimination of urea hydrolysis and as an additive to feed urea as part of animal nutrition, especially of ruminants. The invention further relates to fertilizer compositions containing N- phenylphosphoric triamides and a urea-based fertilizer.
Harnstoff ist ein ursprünglich biogenes Stoffwechselprodukt, das durch das Enzym Urease in Ammoniak und Kohlendioxid gespalten wird. Die Reaktion verläuft außerordentlich schnell und effektiv und ist somit für N-Verluste bei der Anwendung von harnstoffbasierten Düngemitteln verantwortlich. Diese sind besonders hoch, wenn der Boden nicht über eine ausreichende Sorptionskraft verfügt, um das frei gewordene Ammoniak in Form von Ammoniumionen zu binden. Dadurch gehen der Landwirtschaft jährlich beträchtliche Mengen an Stickstoff verloren, die auf diese Weise zur Umweltbelastung beitragen und andererseits einen erhöhten Düngemittelbedarf erfordern.Urea is an originally biogenic metabolite, which is split by the enzyme urease into ammonia and carbon dioxide. The reaction is extremely rapid and effective, and is therefore responsible for N losses in the application of urea-based fertilizers. These are particularly high if the soil does not have sufficient sorption power to bind the liberated ammonia in the form of ammonium ions. As a result, agriculture loses considerable amounts of nitrogen every year, contributing to environmental pollution and requiring increased fertilizer requirements.
Darüber hinaus können unter ungünstigen Klimabedingungen und/oder bei Ausbringung auf leichte Böden spontan hohe Ammoniakkonzentrationen im Boden auftreten, die dann zusätzlich die Keimung und das Auflaufen der Jungpflanzen negativ beeinträchtigen.In addition, under unfavorable climatic conditions and / or when applied to light soils spontaneously high concentrations of ammonia in the soil can occur, which then negatively affect the germination and emergence of young plants.
Da Harnstoff das Stickstoffdüngemittel mit dem prozentual größten N-Gehalt und der weltweit mit Abstand dominierende N-Dünger ist, wird die Suche nach praktikablen Lösungen zur Reduzierung der ureasebedingten N-Verluste verständlich. Um dieses Ziel zu erreichen, ist eine Vielzahl von Lösungen vorgeschlagen worden. Zu nennen sind in diesem Zusammenhang die saure Umhüllung von Harnstoffprills oder -granalien, um auf diese Weise entstehenden Ammoniak durch Salzbildung abfangen zu können oder das Coating mit Substanzen, wodurch Harnstoff verlangsamt freigesetzt wird und somit das entstehende Ammoniak problemlos »abgepuffert« werden kann.Since urea is the largest N-containing nitrogen fertilizer and the world's most abundant N fertilizer, the search for workable solutions to reduce urease-induced N losses becomes understandable. To achieve this goal, a variety of solutions have been proposed. In this context, the acid coating of urea prills or granules, in order to be able to absorb ammonia formed by salt formation, or the coating with substances, whereby urea is released slowed down and thus the resulting ammonia can be easily »buffered«.
Außerdem verursacht die ureasekatalysierte Harnstoff-Hydrolyse durch Spaltung des in Kot und vor allem in Harn befindlichen Harnstoffs in Tierställen zum Teil erhebliche Ammoniaklasten, die - abgesehen von einer Geruchsbelästigung bei entsprechend hoher Konzentration - die Entwicklung und das Wachstum der Tiere negativ beeinflussen.In addition, the urease-catalyzed urea hydrolysis caused by cleavage of urea present in faeces and especially in urine in animal sheds sometimes considerable ammonia loads, which - apart from an odor nuisance at a correspondingly high concentration - adversely affect the development and growth of the animals.
Die N-Verluste aus der ureasekatalysierten Hydrolyse des Harnstoffs und der Nitrifikation können unter ungünstigen Bedingungen, besonders in tropischen und subtropischen Klimaten, bis zu 50 % betragen. Um dieses Verlustpotenzial zu minimieren, werden bedarfsgerecht mehrfach geteilte Düngergaben empfohlen, die jedoch für den Landwirt infolge zusätzlicher Applikationskosten mit erheblichen arbeitswirtschaftlichen Nachteilen und entsprechenden Mehraufwendungen verbunden sind.The N losses from the urease-catalyzed hydrolysis of urea and nitrification may be up to 50% under unfavorable conditions, especially in tropical and subtropical climates. In order to minimize this loss potential, multi-split fertilizer feeds are recommended as needed, which, however, entail significant labor-management disadvantages and corresponding additional expenses for the farmer as a result of additional application costs.
Möglichkeiten zur Einschränkung der Stickstoffverluste bestehen in der gezielten Hemmung der ureasekatalysierten Harnstoff-Hydrolyse auf der einen und der Nitrifikationshemmung auf der anderen Seite. Dabei erscheint im ersten Fall der Einsatz solcher Substanzen aussichtsreich, die zu einer Ureasehemmung führen, wobei sich neben der Anwendung für Düngungszwecke selbstverständlich auch die Anwendung zur Minimierung der Ammoniakbelastung in Tierställen oder deren Zusatz zu Futterharnstoff anbietet.Options for limiting nitrogen losses include the targeted inhibition of urease-catalyzed urea hydrolysis on the one hand and nitrification inhibition on the other. In the first case, the use of such substances appears promising, which lead to urease inhibition, which in addition to the application for fertilization purposes, of course, the application for minimizing the ammonia load in animal sheds or their addition to feed urea offers.
Der Einsatz von Ureaseinhibitoren ist eine effektive Möglichkeit, die unter Normalbedingungen außerordentlich schnell verlaufende enzymatische Harnstoff-Hydrolyse deutlich zu verlangsamen. Durch die Verzögerung dieser Enzymreaktion kann der Düngeharnstoff unzersetzt in tiefere Bodenschichten penetrieren.The use of urease inhibitors is an effective way to significantly slow down the enzymatic urea hydrolysis, which is extremely rapid under normal conditions. Due to the delay of this enzyme reaction, the fertilizer urea can penetrate undecomposed into deeper soil layers.
Damit sind Ammoniakverluste durch das Sorptionspotential der darüber befindlichen Bodenschichten, anders als an der Bodenoberfläche, nahezu ausgeschlossen. Außerdem gelingt es auf diesem Wege, Harnstoff und harnstoffhaltige Dünger für leichte Bodenstandorte verlustfrei zur Anwendung zu bringen.Thus, ammonia losses due to the sorption potential of the soil layers above it, unlike at the soil surface, almost impossible. In addition, it succeeds in this way to bring urea and urea-containing fertilizer for light soil locations lossless application.
In Tierställen kann die Emission von Ammoniak aus Dung und tierischen Exkrementen durch Zusatz eines Ureaseinhibitors auf effektive Weise eingeschränkt werden.In animal houses, the emission of ammonia from manure and animal excrement can be effectively reduced by the addition of a urease inhibitor.
Aus der Sicht der verlustfreien und damit umweltentlastenden Lagerung und Ausbringung von organischen Düngern wie Mist oder Gülle ist der Einsatz von Ureaseinhibitoren, gegebenenfalls auch in Kombination mit Nitrifikationsinhibitoren, gleichfalls eine empfehlenswerte Maßnahme, um die Dünger- und damit Düngungseffizienz von Wirtschaftsdüngern zu erhöhen.From the point of view of lossless and thus environmentally friendly storage and application of organic fertilizers such as manure or liquid manure, the use of urease inhibitors, optionally also in combination with nitrification inhibitors, also a recommended measure to increase the fertilizer and thus fertilization efficiency of manure.
Es ist bekannt, dass speziell in der Tierfütterung von Wiederkäuern die Versorgung der Tiere mit proteinreicher und damit leistungsfördernder Nahrung teilweise ein finanzielles Problem für den Landwirt darstellt, in einigen Regionen der Erde jedoch auch aus klimatischen Gründen ein über das volle Jahr unlösbares Problem ist. Aus heutiger Sicht ist die Substitution pflanzlichen Eiweißes durch Tiermehl in der Wiederkäuerernährung gesundheitspolitisch nicht zu vertreten. Um dieser Situation gerecht zu werden, bietet sich eine teilweise Substitution der hochwertigen proteinreichen pflanzlichen Ernährung der Tiere durch sogenannte »non-protein-nitrogen-Verbindungen« (NPN-Verbindungen) an. Diese Rolle kann der Harnstoff übernehmen, wenn es gelingt, die im Pansen der Tiere ablaufende ureasekatalysierte Harnstoff-Hydrolyse so zu kontrollieren, dass die freigesetzten Ammoniakraten durch anwesende Mikroorganismen sofort zu mikrobiellem Protein verarbeitet werden und demzufolge keine toxischen Effekte auslösen können. Hier bietet sich gleichfalls der Einsatz geeigneter Ureaseinhibitoren an.It is well known that, especially in animal feed for ruminants, feeding animals with protein-rich and thus performance-enhancing food is sometimes a financial problem for the farmer, but in some regions of the world, for climatic reasons, a problem that can not be solved over the whole year. From today's perspective, the substitution of vegetable protein by animal meal in the ruminant nutrition health policy is not responsible. In order to meet this situation, a partial substitution of the high-quality protein-rich plant nutrition of the animals by so-called "non-protein-nitrogen compounds" (NPN compounds) is appropriate. The urea can take on this role if it is possible to control the urease-catalyzed urea hydrolysis taking place in the rumen of the animals in such a way that the released ammonia rates are immediately processed into microbial protein by the presence of microorganisms and consequently can not trigger any toxic effects. The use of suitable urease inhibitors is also suitable here.
Aus der Literatur ist bekannt, dass bestimmte organische, aber auch anorganische Verbindungen die ureasekatalysierte Harnstoff-Hydrolyse zu hemmen vermögen (vgl.
Mit der Entdeckung der Phosphorsäureesterdiamide (
Bei genauer Prüfung dieser Substanzen zeigt es sich, dass einige relativ hydrolyseanfällig sind, wodurch vor allem ihre Wirkungsdauer und somit ihre Anwendbarkeit erheblich eingeschränkt ist. Zum anderen sind sie teilweise nur in geringer Ausbeute oder mittels aufwendiger Herstellungsverfahren erhältlich, so dass eine vertretbare Ökonomie nicht gegeben ist. Aufgrund der Hydrolyseanfälligkeit des NBTPT und dessen Instabilität in Kombination mit harnstoffbasierten Düngemitteln kommt dieser Wirkstoff als Flüssigformulierung zum Einsatz, wobei die Formulierung unmittelbar vor der Düngerapplikation mit dem harnstoffbasierten Düngemittel gemischt wird, was äußerst unökonomisch ist. Eine gleichmäßige Wirkstoffverteilung auf den Düngergranalien kann so kaum gewährleistet werden. Darüber hinaus versagt NBTPT unter anaeroben Bedingungen im Reisanbau, also gerade dort, wo die höchsten Stickstoffverluste und Ammoniakemissionen zu verzeichnen sind, da die Bildung des Sauerstoffanalogons des NBTPT und damit des eigentlichen Ureaseinhibitors nicht oder nur langsam möglich ist (vgl.
Weitere, die Anwendung der erwähnten Verbindungen beeinflussende Nachteile sind, dass sie ein anderes Migrationsverhalten als Harnstoff haben. Dadurch wird der Inhibitor vom Substrat Harnstoff getrennt, was zur Beeinträchtigung der Enzymhemmung führen kann. Möglich ist aber auch, dass ursprünglich wirksame Ureaseinhibitoren, wenn sie mit Boden in Kontakt kommen, ihre Inhibitorwirkung durch Reaktion mit Bodenbestandteilen oder Fixierung an diese verlieren.Other disadvantages affecting the use of the mentioned compounds are that they have a different migration behavior than urea. As a result, the inhibitor is separated from the substrate urea, which can lead to impairment of the enzyme inhibition. But it is also possible that originally effective urease inhibitors, when in contact with soil, lose their inhibitory effect by reaction with soil components or fixation to them.
Neben den N-Verlusten durch unkontrollierte ureasekatalysierte Hydrolyse des Harnstoffs geht Stickstoff in Form von Nitrat verloren, das durch Auswaschung oder Verlagerung in tiefere Bodenschichten der Pflanzenernährung entzogen wird. Darüber hinaus können diese N-Verluste noch erhöht werden, wenn im Verlaufe der raschen Nitrifikation von Ammoniumionen relativ große Mengen an Nitrat gebildet werden, die ihrerseits durch einsetzende Denitrifikation in molekularen Stickstoff überführt werden können und damit gleichfalls für die pflanzliche Ernährung nicht mehr verfügbar sind.In addition to the N losses due to uncontrolled urease-catalyzed hydrolysis of urea, nitrogen is lost in the form of nitrate, which is removed by leaching or transfer to deeper soil layers of plant nutrition. In addition, these N losses can be increased even if in the course of the rapid nitrification of ammonium ions relatively large amounts of nitrate are formed, which in turn can be converted by incipient denitrification in molecular nitrogen and thus are also no longer available for plant nutrition.
Als Nitrifikationsinhibitoren sind beispielsweise substituierte Pyrazole (
Zur umfassenden Minimierung der Stickstoffverluste bei der Anwendung von harnstoffbasierten Düngemitteln bietet sich die Anwendung von Ureaseinhibitoren in Kombination mit Nitrifikationsinhibitoren an. Untersuchungen dazu haben jedoch gezeigt, dass Urease- und Nitrifikationsinhibitoren nicht beliebig miteinander kombiniert werden können, da unter bestimmten Bedingungen sich die zusätzliche Anwendung eines Nitrifikationsinhibitors zum Ureasehemmstoff negativ auf die beabsichtigte Senkung der Ammoniakverluste auswirken kann (
In der
Der vorliegenden Erfindung lag daher die Aufgabe zugrunde, solche Ureaseinhibitoren für die Praxis zur Verfügung zu stellen, die bei der Anwendung mit Düngeharnstoff oder anderen harnstoffbasierten Düngern in der Lage sind, die enzymkatalysierte Harnstoff-Hydrolyse auf ein solches Maß zu beschränken, dass daraus resultierende Stickstoffverluste in Form von Ammoniak nahezu auszuschließen sind bzw. die Ammoniaklast in Tierställen durch spontane Zersetzung des Harnstoffs deutlich reduziert wird. Die neuen Ureaseinhibitoren sollen ohne Wirkungseinbußen mit Nitrifikationsinhibitoren kombinierbar sein, um eine weitere Verbesserung der N-Ausnutzung in harnstoffbasierten Düngemitteln zu erreichen.The present invention therefore an object of the invention to provide such urease inhibitors for the practice available when used with fertilizer or other urea-based fertilizers are able to limit the enzyme-catalyzed urea hydrolysis to such an extent that the resulting nitrogen losses in the form of ammonia are almost impossible or the ammonia load in animal houses by spontaneous decomposition of urea is significantly reduced. The new urease inhibitors should be combinable with nitrification inhibitors without any loss of effect in order to achieve a further improvement in N utilization in urea-based fertilizers.
Gleichermaßen sollen diese Ureaseinhibitoren die im Pansen von Wiederkäuern ablaufende Harnstoffspaltung bei Einsatz von Harnstoff im Rahmen der Tierfütterung so verlangsamen, dass die Tiere durch sonst erfolgende Ammoniak-Intoxikationen keine Schäden erleiden und andererseits den auf diese Weise angebotenen Stickstoff für die körpereigene Proteinbiosynthese verwerten können.Likewise, these urease inhibitors should slow down the urea cleavage in the rumen of ruminants when using urea as part of animal feeding so that the animals suffer no damage from otherwise taking ammonia intoxications and on the other hand can utilize the thus offered nitrogen for the body's protein biosynthesis.
Ein weiteres Anwendungsgebiet ist die Medizin. Die Ureaseinhibitoren können zur Prophylaxe oder Therapie von Störungen oder Erkrankungen eingesetzt werden, die direkt oder indirekt durch Ureaseaktivität induziert oder begünstigt werden. Beispiele dafür sind die Katheterverkrustung, entzündliche und ulzeröse Magen- und Darmerkrankungen, Urolithiasis, Pyelonephritis, Nephrolithiasis, Ammoniak-Encephalopathie, hepatische Encephalopathie, hepatisches Koma, Harnwegsinfektionen und gastrointestinale Infektionen. Diese können beispielsweise durch Urease produzierende Mikroorganismen wie Helicobacter pylori verursacht werden.Another area of application is medicine. The urease inhibitors can be used for the prophylaxis or therapy of disorders or diseases that are induced or promoted directly or indirectly by urease activity. Examples include catheter encrustation, inflammatory and ulcerative gastric and intestinal diseases, urolithiasis, pyelonephritis, nephrolithiasis, ammonia encephalopathy, hepatic encephalopathy, hepatic coma, urinary tract infections, and gastrointestinal infections. These can be caused for example by urease-producing microorganisms such as Helicobacter pylori.
Diese Aufgaben werden erfindungsgemäß durch die Bereitstellung und Verwendung der N-(2-Nitrophenyl)phosphorsäuretriamide mit den in Anspruch 1 definierten Strukturen gelöst.These objects are achieved by the provision and use of the N - (2-nitrophenyl) phosphoric triamides having the structures defined in claim 1.
Es hat sich nämlich überraschenderweise gezeigt, dass die erfindungsgemäß bereitgestellten und eingesetzten N-(2-Nitrophenyl)phosphorsäuretriamide bei geeigneter Substitution am Phenylrest hocheffektive Ureaseinhibitoren mit außerordentlich langanhaltender Wirkung darstellen. Neben einer ausreichenden Hydrolysebeständigkeit sind die erfindungsgemäßen N-(2-Nitrophenyl)phosphorsäuretriamide außerdem technisch problemlos und kostengünstig aus einfachen Ausgangsstoffen herstellbar. Die erfindungsgemäßen N-(2-Nitrophenyl)phosphorsäuretriamide sind außerdem mit gebräuchlichen Verfahren leicht in Harnstoff oder harnstoffbasierte Düngemitteln einarbeitbar, womit eine effiziente Ausbringung zusammen mit dem Düngemittel bzw. Verfütterung an Wiederkäuer möglich ist. Sie sind sowohl ausreichend wasserlöslich als auch gut öllöslich, was ebenfalls nicht vorhersehbar war. Ein weiterer Vorteil der erfindungsgemäßen N-(2-Nitrophenyl)phosphorsäuretriamide ist deren problemlose Kombinierbarkeit mit Nitrifikationsinhibitoren.It has surprisingly been found that the N - (2-nitrophenyl) phosphoric triamides provided and used according to the invention, with suitable substitution on the phenyl radical, are highly effective urease inhibitors with an extremely long-lasting effect. With ample hydrolysis north of the invention are - (2-nitrophenyl) phosphoric also technical problems and cost-effectively from simple starting materials. The N inventive - (2-nitrophenyl) phosphoric come equipped with common Method easily incorporated into urea or urea-based fertilizers, which is an efficient application together with the fertilizer or feeding to ruminants possible. They are both sufficiently water-soluble and well oil-soluble, which was also unpredictable. Another advantage of the invention N - (2-nitrophenyl) phosphoric whose easy combinability with nitrification inhibitors.
Die Erfindung betrifft ferner Verfahren zur Herstellung der erfindungsgemäßen N-(2-Nitrophenyl)phosphorsäuretriamide wie in Anspruch 3 definiert, Zusammensetzungen, die diese N-(2-Nitrophenyl)phosphorsäuretriamide enthalten, wie in Anspruch 3 definiert, eine Düngemittelzusammensetzung wie in Anspruch 7 definiert sowie die in den Ansprüchen 10 bis 16 definierten Verwendungen.The invention further relates to methods for the preparation of N invention - (2-nitrophenyl) phosphoric acid triamides as defined in claim 3, compositions containing these n - (2-nitrophenyl) phosphoric acid triamides as defined in claim 3, a fertilizer composition as defined in claim 7 and the uses defined in claims 10 to 16.
Weitere vorteilhafte und/oder bevorzugte Ausführungsformen der Erfindung sind Gegenstand der Unteransprüche.Further advantageous and / or preferred embodiments of the invention are the subject of the dependent claims.
Die erfindungsgemäßen N-(2-Nitrophenyl)phosphorsäuretriamide als Ureaseinhibitoren besitzen die allgemeine Formel (I):
- X = Sauerstoff oder Schwefel
- R1, R2, R3, R4 = unabhängig voneinander Wasserstoff, C1-C8-Alkyl/Heteroalkyl, C2-C8-Alkenyl/Heteroalkenyl, C2-C8-Alkinyl/Heteroalkinyl. C3-C8-Cycloalkyl/Heterocycloalkyl, C3-C8-Cycloalkenyl/Heterocycloalkenyl, C6-C10-Aryl/C5-C10-Heteroaryl, Aralkyl, Heteroarylalkyl, Alkaryl, Alkheteroaryl, Alkoxy, Aryloxy, Hetaryloxy, Alkylthio, Arylthio, Hetarylthio, Acyl, Aroyl, Hetaroyl, Acyloxy, Aroyloxy, Hetaroyloxy, Alkoxycarbonyl, Aryloxycarbonyl, Hetaryloxycarbonyl, Alkylsulfonyl, Fluor, Chlor, Brom, Iod, Cyano, Nitro, Sulfo, Carbonyl, Carboxy, Carbamoyl, Sulfamoyl bedeuten,
wobei die Reste R1-R4 gegebenenfalls selber und unabhängig voneinander mit einer oder mehreren der oben genannten Gruppen sowie durch Amino, Alkylamino, Dialkylamino, Hydroxy, Mercapto substituiert sein können,
sowie Salze, Tautomere und Metallkomplexe von Verbindungen der allgemeinen Formel (I), die ureaseinhibierende Wirkung haben.The N inventive - (2-nitrophenyl) phosphoric as urease inhibitors have the general formula (I):
- X = oxygen or sulfur
- R 1 , R 2 , R 3 , R 4 = independently of one another are hydrogen, C 1 -C 8 -alkyl / heteroalkyl, C 2 -C 8 -alkenyl / heteroalkenyl, C 2 -C 8 -alkynyl / heteroalkynyl. C 3 -C 8 -cycloalkyl / heterocycloalkyl, C 3 -C 8 -cycloalkenyl / heterocycloalkenyl, C 6 -C 10 -aryl / C 5 -C 10 -heteroaryl, aralkyl, heteroarylalkyl, alkaryl, alkheteroaryl, alkoxy, aryloxy, hetaryloxy, Alkylthio, arylthio, hetarylthio, acyl, aroyl, hetaroyl, acyloxy, aroyloxy, hetaroyloxy, alkoxycarbonyl, aryloxycarbonyl, hetaryloxycarbonyl, alkylsulfonyl, fluorine, chlorine, bromine, iodine, cyano, nitro, sulfo, carbonyl, carboxy, carbamoyl, sulfamoyl,
where the radicals R 1 -R 4 may optionally themselves and independently of one another be substituted by one or more of the abovementioned groups and by amino, alkylamino, dialkylamino, hydroxy, mercapto,
and salts, tautomers and metal complexes of compounds of the general formula (I) which have urease-inhibiting activity.
Die Reste R1-R4 können gegebenenfalls selber und unabhängig voneinander mit einer oder mehreren der oben genannten Gruppen sowie durch Amino, Alkylamino, Dialkylamino, Hydroxy, Mercapto substituiert sein. Zwei benachbarte Reste R (z.B. R1 und R2) können miteinander über eine Alkylen- bzw. Alkenylen-Kette unter Bildung eines 5-6-gliedrigen, ggf. aromatischen Ringsystems verknüpft sein, welches ggf. ein oder mehrere Heteroatome, wie Sauerstoff, Stickstoff oder Schwefel enthalten und durch oben genannte Gruppen substituiert sein kann.The radicals R 1 -R 4 may optionally be substituted independently and independently of one another by one or more of the abovementioned groups and by amino, alkylamino, dialkylamino, hydroxy, mercapto. Two adjacent radicals R (for example R 1 and R 2 ) may be linked to one another via an alkylene or alkenylene chain to form a 5-6-membered, optionally aromatic ring system which may contain one or more heteroatoms, such as oxygen, Contain nitrogen or sulfur and may be substituted by the above groups.
Ein bevorzugtes N-(2-Nitrophenyl)phosphorsäuretriamide der vorliegenden Erfindung entspricht der Formel (II):
Außerdem umfasst die Erfindung Salze, Tautomere und Metallkomplexe von Verbindungen der allgemeinen Formel (I) oder (II), die ureaseinhibierende Wirkung haben.In addition, the invention includes salts, tautomers and metal complexes of compounds of the general formula (I) or (II) which have urease-inhibiting activity.
Selbstverständlich wird der Fachmann die in der allgemeinen Formel (I) angegebenen Reste bzw. Gruppen so auswählen, dass keine unmöglichen Moleküle entstehen, z.B. chemisch oder sterisch unmögliche.Of course, those skilled in the art will select the radicals or groups given in the general formula (I) such that no impossible molecules are formed, e.g. chemically or sterically impossible.
Die im folgenden erwähnten Alkyl-, Alkenyl- oder Alkinyl-Gruppen mit der entsprechenden Kohlenstoffanzahl können geradkettig oder verzweigt und einfach oder mehrfach ungesättigt sein.The alkyl, alkenyl or alkynyl groups with the corresponding carbon number mentioned below may be straight-chain or branched and mono- or polyunsaturated.
Im folgenden wird zwar zur Vermeidung unnötiger Redundanz auch gelegentlich der Einfachheit halber nur der Begriff »Alkyl-Gruppe«, »Heteroalkyl-Gruppe« oder »Cycloalkyl-Gruppe« etc. verwendet, jedoch sollen jeweils die entsprechenden ungesättigten Gruppen umfaßt sein. Dem Fachmann ist klar, daß Alkenyl- oder Alkinyl-Gruppen mindestens 2 Kohlenstoffatome und cyclische Kohlenwasserstoff-Gruppen mindestens 3 Kohlenstoffatome aufweisen müssen.In the following, although the term "alkyl group", "heteroalkyl group" or "cycloalkyl group", etc. is used occasionally for the sake of simplicity, to avoid unnecessary redundancy, the corresponding unsaturated groups should be included in each case. It will be understood by those skilled in the art that alkenyl or alkynyl groups must have at least 2 carbon atoms and cyclic hydrocarbon groups must have at least 3 carbon atoms.
Der Begriff »Alkyl« bezieht sich, und zwar in jeder Kombination mit beliebigen anderen Gruppen, insbesondere auf eine Alkyl-Gruppe, die 1 bis 8 Kohlenstoffatome aufweist, z.B. eine Methyl-, Ethyl-, n-Propyl-, Isopropyl-, n-Butyl-, Isobutyl-, tert-Butyl, Amyl, Isoamyl, n-Hexyl-, 2,2-Dimethylbutyl- oder n-Octyl-Gruppe.The term "alkyl" refers to any combination with any other groups, especially an alkyl group having from 1 to 8 carbon atoms, e.g. a methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, amyl, isoamyl, n-hexyl, 2,2-dimethylbutyl or n-octyl group.
Der Begriff »Alkenyl« bezieht sich, und zwar in jeder Kombination mit beliebigen anderen Gruppen, insbesondere auf eine Alkenyl-Gruppe, die 2 bis 8 Kohlenstoffatome aufweist, z.B. eine Ethenyl-, n-Propenyl-, Isopropenyl-, n-Butenyl-, Isobutenyl-, tert-Butenyl, n-Hexenyl-, 2,2-Dimethylbutenyl-, n-Octenyl-, Allyl-, Isoprenyl- oder Hex-2-enyl-Gruppe.The term "alkenyl" refers to any combination with any other groups, especially an alkenyl group having from 2 to 8 carbon atoms, e.g. an ethenyl, n-propenyl, isopropenyl, n-butenyl, isobutenyl, tert-butenyl, n-hexenyl, 2,2-dimethylbutenyl, n-octenyl, allyl, isoprenyl or hex-2 enyl group.
Der Begriff »Alkinyl« bezieht sich, und zwar in jeder Kombination mit beliebigen anderen Gruppen, insbesondere auf eine Alkinyl-Gruppe, die 2 bis 8 Kohlenstoffatome aufweist, z.B. eine Ethinyl-, n-Propinyl-, Isopropinyl-, n-Butinyl-, Isobutinyl-, tert-Butinyl, n-Hexinyl-, 2,2-Dimethylbutinyl- oder n-Octinyl-Gruppe.The term "alkynyl" refers to any combination with any other groups, especially an alkynyl group having from 2 to 8 carbon atoms, e.g. an ethynyl, n-propynyl, isopropynyl, n-butynyl, isobutinyl, tert-butynyl, n-hexynyl, 2,2-dimethylbutynyl or n-octynyl group.
Der Begriff »Heteroalkyl« bezieht sich bzgl. des Alkylteils auf eine oben definierte Alkyl-Gruppe, soll aber auch eine entsprechende Heteroalkenyl- oder Heteroalkinyl-Gruppe umfassen, in der ein oder mehrere Kohlenstoffatome durch mindestens ein Sauerstoff-, Stickstoff-, Phosphor- oder Schwefelatom ersetzt sind.The term "heteroalkyl" refers with respect to the alkyl part to an alkyl group as defined above, but should also include a corresponding heteroalkenyl or heteroalkynyl group in which one or more carbon atoms by at least one oxygen, nitrogen, phosphorus or Sulfur atom are replaced.
Es ist klar, daß sämtliche der oben definierten Gruppen mit sich selbst oder anderen der oben definierten Gruppen substituiert sein können, sofern die ureaseinhibierende Wirkung erhalten bleibt.It is clear that all of the groups defined above may be substituted with themselves or with other groups as defined above, provided that the urease-inhibiting effect is maintained.
Der Begriff »Aryl« bezieht sich auf eine aromatische cyclische Gruppe, die einen oder mehrere Ringe aufweist, und durch ein Gerüst gebildet wird, das 6 bis 10 Ringkohlenstoffatome enthält. Selbstverständlich kann im Falle von mehreren Ringen einer oder auch mehrere Ringe ganz oder teilweise hydriert sein (ein Beispiel dafür ist die 1,2,3,4,-Tetrahydro-naphthalen-1-yl-Gruppe). Außerdem kann eine Aryl-Gruppe durch Alkyl- oder Heteroalkyl-Gruppen (jeweils wie oben definiert) substituiert sein. Beispiele sind eine Phenyl-, Naphthyl-, Inden-, 2-, 3- oder 4-Methoxyphenyl-, 2-, 3-oder 4-Ethoxyphenyl-, 4-Carboxyphenylalkyl- oder 4-Hydroxyphenyl-Gruppe.The term "aryl" refers to an aromatic cyclic group having one or more rings and is formed by a skeleton containing 6 to 10 ring carbon atoms. Of course, in the case of several rings, one or more rings may be completely or partially hydrogenated (an example being the 1,2,3,4-tetrahydro-naphthalen-1-yl group). In addition, an aryl group may be substituted by alkyl or heteroalkyl groups (each as defined above). Examples are a phenyl, naphthyl, indene, 2-, 3- or 4-methoxyphenyl, 2-, 3- or 4-ethoxyphenyl, 4-carboxyphenylalkyl or 4-hydroxyphenyl group.
Die Begriffe »Aralkyl« bzw. »Heteroarylalkyl« beziehen sich auf Gruppen, die entsprechend den obigen bzw. folgenden Definitionen sowohl Aryl- bzw. Heteroaryl-(weiter unten definiert) wie auch Alkyl- und/oder Heteroalkyl- (auch die entsprechenden Alkylen/Heteroalkylen- und Alkinyl/Heteroalkinyl-Gruppen) und/oder carbocyclische Gruppen (weiter unten definiert) und/oder Heterocycloalkyl-Ringsysteme (weiter unten definiert) umfassen, z.B. eine Tetrahydroisochinolinyl-, Benzyl-, 2- oder 3-Ethylindolyl- oder 4-Methylpyridino-Gruppe.The terms "aralkyl" or "heteroarylalkyl" refer to groups which according to the above or following definitions are both aryl or heteroaryl (defined below) as well as alkyl and / or heteroalkyl (also the corresponding alkylene / Heteroalkylene and alkynyl / heteroalkynyl groups) and / or carbocyclic groups (defined below) and / or heterocycloalkyl ring systems (defined below), eg a tetrahydroisoquinolinyl, benzyl, 2- or 3-ethyl-indolyl or 4-methylpyridino group.
Die Begriffe »Aralkyl« bzw. »Heteroarylalkyl« sollen, zur Vermeidung unnötiger Redundanz, auch die Begriffe »Alkaryl« bzw. »Alkheteroaryl« umfassen.The terms "aralkyl" and "heteroarylalkyl" are also intended to include the terms "alkaryl" and "alkheteroaryl" to avoid unnecessary redundancy.
Der Begriff »Cycloalkyl« bzw. »carbocyclisch« bezieht sich auf eine gesättigte oder teilweise ungesättigte, cyclische, ggf. verzweigte, Gruppe, die einen oder mehrere Ringe aufweist, die ein Gerüst bilden, welches 3 bis 8 Kohlenstoffatome enthält, z.B. eine Cyclopropyl-, Cyclobutyl-, Cyclopentyl-, Cyclohexyl-, Tetralin-, Cyclopentenyl-oder Cyclohex-2-enyl-Gruppe.The term "cycloalkyl" or "carbocyclic" refers to a saturated or partially unsaturated, cyclic, optionally branched, group having one or more rings forming a skeleton containing from 3 to 8 carbon atoms, e.g. a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetralin, cyclopentenyl or cyclohex-2-enyl group.
Der Begriff »Heterocycloalkyl« bezieht sich auf die oben definierten Cycloalkyl- bzw. carbocylischen Gruppen, bei denen ein oder mehrere Kohlenstoffatome durch ein oder mehrere Sauerstoff-, Stickstoff-, Phosphor- oder Schwefelatome ersetzt sind. Konkrete Beispiele sind Aziridin-, Furan-, Pyrrolidin-, Piperidin-, Morpholin-, Oxazolidin-, Thiazolidin-, N-Methylpiperazino oder N-Phenylpiperazin-Gruppen.The term "heterocycloalkyl" refers to the above-defined cycloalkyl or carbocyclic groups in which one or more carbon atoms are replaced by one or more oxygen, nitrogen, phosphorus or sulfur atoms. Specific examples are aziridine, furan, pyrrolidine, piperidine, morpholine, oxazolidine, thiazolidine, N-methylpiperazino or N-phenylpiperazine groups.
Der Begriff »Heteroaryl« bezieht sich auf eine Aryl-Gruppe mit 5 bis 10 Ringatomen, in der ein oder mehrere Kohlenstoffatome durch ein Sauerstoff-, Stickstoff-, Phosphor- oder Schwefelatom ersetzt sind. Beispiele sind Pyrrol-, Furan-, Thiophen-, Pyrazol-, Isoxazol-, Isothiazol-, Imidazol-, Oxazol-, Thiazol-, 1,2,4-Triazol-, 1,2,4-Oxadiazol-, 1,2,4-Thiadiazol-, 1,3,4-Oxadiazol-, 1,3,4-Thiadiazol-, 1,2,5-Oxadiazol-, 1,2,5-Thiadiazol, Tetrazol, Pyridin-, Pyridazin-, Pyrimidin-, Pyrazin-, 1,2,3-Triazin-, 1,2,4-Triazin-, 1,3,5-Triazin- und Indol-Gruppen.The term "heteroaryl" refers to an aryl group of 5 to 10 ring atoms in which one or more carbon atoms are replaced by an oxygen, nitrogen, phosphorus or sulfur atom. Examples are pyrrole, furan, thiophene, pyrazole, isoxazole, isothiazole, imidazole, oxazole, thiazole, 1,2,4-triazole, 1,2,4-oxadiazole, 1,2 , 4-thiadiazole, 1,3,4-oxadiazole, 1,3,4-thiadiazole, 1,2,5-oxadiazole, 1,2,5-thiadiazole, tetrazole, pyridine, pyridazine, pyrimidine , Pyrazine, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine and indole groups.
Es sei nochmal darauf hingewiesen, daß sämtliche der oben definierten Gruppen sowohl mit sich selbst als auch mit anderen der oben definierten Gruppen substituiert sein können, sofern die ureaseinhibierende Wirkung erhalten bleibt.It should again be noted that all of the groups defined above may be substituted both with themselves and with other groups defined above, provided that the urease-inhibiting effect is maintained.
Die erfindungsgemäßen Verbindungen I sind durch analoge Anwendung bekannter Verfahren zugänglich (
- a1) 2-Nitroaniline oder deren Hydrochloride mit Phosphorylchlorid (POCl3) oder Thiophosphorylchlorid (PSCl3), gegebenenfalls in Anwesenheit eines organischen Lösungsmittels und einer tertiären Base, bei Temperaturen von 0 bis 150 °C, gegebenenfalls unter Schutzgasatmosphäre, entsprechend Gleichung (1) zu N-(2-Nitrophenyl)phosphorsäureamiddichloriden des Typs (A) umsetzt, wobei Verbindungen (A) mit X = S alternativ auch durch Schwefelung der entsprechenden Sauerstoffderivate erhalten werden können,
- a2) Phosphorpentachlorid (PCl5) mit einem 2-Nitroanilin, in annähernd äquimolarem Verhältnis, gegebenenfalls in einem inerten organischen Lösemittel und gegebenenfalls unter Schutzgasatmosphäre bei 0 bis 150°C entsprechend Gleichung (2) zu Verbindungen des Typs (B) reagieren lässt, welche, gegebenenfalls ohne weitere Isolation, mit einer annähernd äquimolaren Menge Ameisensäure oder Wasser zu N-(2-Nitrophenyl)phosphorsäureamiddichloriden des Typs (A) umgesetzt werden, wobei Verbindungen (A) mit X = S durch Schwefelung der entsprechenden Sauerstoffderivate erhalten werden können,
- b) die in Stufe a1) oder a2) gebildeten Verbindungen des Typs (A) mit Ammoniak, gegebenenfalls in einem inerten organischen Lösemittel, bei Temperaturen von -80 bis 30 °C entsprechend Gleichung (3) zum gewünschten Endprodukt reagieren lässt:
- a 1 ) 2-nitroanilines or their hydrochlorides with phosphoryl chloride (POCl 3 ) or thiophosphoryl chloride (PSCl 3 ), optionally in the presence of an organic solvent and a tertiary base, at temperatures of 0 to 150 ° C, optionally under a protective gas atmosphere, according to equation (1 ) to N - (2-nitrophenyl) phosphoric acid amide dichlorides of the type (A), wherein compounds (A) with X = S can alternatively also be obtained by sulfurization of the corresponding oxygen derivatives,
- a 2 ) phosphorus pentachloride (PCl 5 ) with a 2-nitroaniline, in approximately equimolar ratio, optionally in an inert organic solvent and optionally under a protective gas atmosphere at 0 to 150 ° C according to equation (2) reacts to compounds of type (B), which, optionally without further isolation, are reacted with an approximately equimolar amount of formic acid or water to give N- (2-nitrophenyl) phosphoric acid amide dichlorides of type (A), whereby compounds (A) with X = S can be obtained by sulfurization of the corresponding oxygen derivatives,
- b) reacting the compounds of type (A) formed in stage a 1 ) or a 2 ) with ammonia, if appropriate in an inert organic solvent, at temperatures of -80 to 30 ° C. in accordance with equation (3) to give the desired end product:
Die erfindungsgemäßen N-(2-Nitrophenyl)phosphorsäuretriamide oder diese enthaltende Zusammensetzungen weisen bei geeigneter Substitution am Phenylrest eine für praktische Belange hervorragende Inhibitionswirkung auf, wodurch sie die enzymatische Harnstoff-Hydrolyse so verlangsamen oder vorübergehend ausschalten können, dass Ammoniakverluste im Rahmen von Düngungsmaßnahmen unter Verwendung organischer und/oder mineralischer harnstoffhaltiger Stickstoffdünger auf ein Minimum reduziert werden bzw. das Auftreten schädlicher oder lästiger Ammoniakkonzentrationen in der Tierhaltung ausgeschlossen wird, beispielsweise durch Harnstoffabbau in tierischen Exkrementen oder durch den Abbau von Futterharnstoff im Pansen im Rahmen der Wiederkäuerernährung.The N invention - (2-nitrophenyl) phosphoric or compositions containing the same have with appropriate substitution on the phenyl radical excellent for practical purposes inhibitory effect on, whereby they can slow down or the enzymatic urea hydrolysis so temporarily turn that ammonia losses under fertilizer treatments using organic and / or mineral urea-containing nitrogen fertilizer are reduced to a minimum or the occurrence of harmful or troublesome ammonia concentrations in animal husbandry is excluded, for example by urea degradation in animal excreta or by the degradation of feed urea in the rumen as part of the ruminant diet.
Dabei ist es unerheblich, ob sich die Wirkung der erfindungsgemäßen N-(2-Nitrophenyl)phosphorsäuretriamide oder diese enthaltenden Zusammensetzungen auf Düngungsmaßnahmen oder auf vorbeugend Maßnahmen zur Vermeidung hoher Ammoniakkonzentrationen in Tierställen erstreckt oder aber für den Einsatz von Futterharnstoff im Rahmen der Wiederkäuerernährung genutzt wird.It is irrelevant whether the effect of N inventive - (2-nitrophenyl) phosphoric or compositions containing them extends or fertilizer treatments or preventive measures to avoid high concentrations of ammonia in livestock barns but is used for the use of feed urea within the framework of ruminant nutrition.
Die erfindungsgemäßen Verbindungen werden vorzugsweise gemeinsam mit harnstoffbasierten Düngemitteln, vorzugsweise in einer Menge von 0,001 bis 10 Gew.-%, bezogen auf das Gewicht des harnstoffbasierten Düngemittels, ausgebracht oder dem Futterharnstoff bzw. den in Tierställen anfallenden tierischen Ausscheidungen zugesetzt. Dabei ist es beispielsweise im Rahmen von Düngungsmaßnahmen unwesentlich, ob sie oberflächig vorher auf den Dünger aufgebracht, darin inkorporiert oder gemeinsam oder in vertretbarem Zeitraum getrennt von harnstoffhaltigen Düngemitteln ausgebracht werden.The compounds according to the invention are preferably applied together with urea-based fertilizers, preferably in an amount of 0.001 to 10% by weight, based on the weight of the urea-based fertilizer, or added to the feed urea or animal waste arising in animal stalls. It is immaterial, for example, in the context of fertilization measures, whether they are superficially previously applied to the fertilizer, incorporated therein or applied together or in a reasonable time separately from urea-containing fertilizers.
Ein weiterer Gegenstand der Erfindung sind somit Zusammensetzungen, die die erfindungsgemäß eingesetzten N-(2-Nitrophenyl)phosphorsäuretriamide und ein harnstoffbasiertes mineralisches und/oder organisches Düngemittel enthalten.Another object of the invention are thus compositions containing the inventively used N - (2-nitrophenyl) phosphoric triamides and a urea-based mineral and / or organic fertilizer.
Die erfindungsgemäß vorgeschlagenen Verbindungen können zur gleichzeitigen Verhinderung bzw. Einschränkung der ureasekatalysierten Harnstoff-Hydrolyse sowie der Nitrifikation auf die oben beschriebene Weise mit einer oder mehreren der folgenden Verbindungen, bei denen es sich um Nitrifikationsinhibitoren handelt, beispielsweise in einer Menge von 0,01 bis 10 Gew.-%, bezogen auf das Gewicht des harnstoffbasierten Düngemittels, kombiniert werden:
- a) Pyrazol-Derivate der allgemeinen Formel (IV), oder Salze oder Komplexverbindungen davon:
- R7, R8, R9 unabhängig voneinander Wasserstoff, Halogen, C1-C8-Alkyl, oder C3-C8-Cycloalkyl
und - A den Rest H
oder den Rest
oder den Rest
-CH2-B mit B = (Di)alkylamino, - R12 = H oder
- R7, R8, R9 unabhängig voneinander Wasserstoff, Halogen, C1-C8-Alkyl, oder C3-C8-Cycloalkyl
- b) 1H-1,2,4-Triazole, oder deren Salze oder Komplexverbindungen,
- c) Dicyandiamid.
- a) pyrazole derivatives of the general formula (IV), or salts or complex compounds thereof:
- R 7 , R 8 , R 9 independently of one another are hydrogen, halogen, C 1 -C 8 -alkyl, or C 3 -C 8 -cycloalkyl
and - A the rest H
or the rest
or the rest
-CH 2 -B with B = (di) alkylamino, - R 12 = H or
- R 7 , R 8 , R 9 independently of one another are hydrogen, halogen, C 1 -C 8 -alkyl, or C 3 -C 8 -cycloalkyl
- b) 1H-1,2,4-triazoles, or their salts or complex compounds,
- c) dicyandiamide.
Zur Verwendung als Ureaseinhibitoren, beispielsweise zur Senkung der Stickstoffverluste bei der Düngung mit Düngeharnstoff oder harnstoffbasierten Düngern oder zur Verminderung der Ammoniakbelastung aus dem Dung bzw. den tierischen Exkrementen in Tierställen oder zur Vermeidung toxischer Effekte beim Einsatz von Futterharnstoff können die erfindungsgemäß geeigneten Verbindungen auf verschiedene Art und Weise ausgebracht bzw. aufgebracht werden.For use as urease inhibitors, for example to reduce the nitrogen losses during fertilization with fertilizer or urea-based fertilizers or to reduce the ammonia load from the manure or animal excrements in animal sheds or to avoid toxic effects when using feedurea, the compounds suitable according to the invention can be used in various ways and applied or applied.
Die erfindungsgemäßen Verbindungen können in den Harnstoff oder in harnstoffhaltige Düngemittel vor oder während der Granulation aus der schmelzflüssigen Phase eingearbeitet werden. Weiterhin können sie auf die Oberfläche der Harnstoff- bzw. Düngemittelgranalien aufgebracht oder flüssigen harnstoffhaltigen Düngemitteln zugesetzt werden. Schließlich ist die Zugabe der Ureaseinhibitoren zu organischen harnstoffhaltigen Düngern wie Dung oder Gülle möglich. Darüber hinaus können die erfindungsgemäßen Verbindungen auch zusätzlich zur Ausbringung harnstoffbasierter Düngemittel in einem vor- oder nachgelagerten Arbeitsschritt separat auf dem Feld ausgebracht werden. Die erfindungsgemäßen Verbindungen können dabei in reiner Form als pulverfömiger Stoff, Granulat oder Schmelze, wässrige Lösung oder als spezielle Formulierung, versetzt mit den üblichen und dem Fachmann bekannten Hilfs-, Träger- und Streckstoffen oder einer Kombination dieser Mittel, eingesetzt werden. Dabei ist es unerheblich, ob der wirksame Inhaltsstoff in flüssiger Form als z. B. Lösung, Emulsion oder Suspension oder in fester Form als stäub- oder dispergierbares Pulver formuliert wird. Benetzbare Pulver, emulgierbare Konzentrate und Suspensionskonzentrate enthalten gewöhnlich, aber nicht notwendigerweise, oberflächenaktive Mittel, z. B. ein Benetzungs-, Dispersions-, Emulgierungs oder Suspensionsmittel. Die jeweiligen Formulierungsverfahren entsprechen dem Stand der Technik und sind dem Fachmann bekannt.The compounds of the invention may be incorporated into the urea or urea-containing fertilizers prior to or during granulation from the molten phase. Furthermore, they can be applied to the surface of the urea or fertilizer granules or added to liquid urea-containing fertilizers. Finally, it is possible to add the urease inhibitors to organic urea-containing fertilizers, such as manure or manure. In addition, the compounds according to the invention can also be applied separately in the field in addition to the application of urea-based fertilizers in a preceding or subsequent work step. The compounds according to the invention can be used in pure form as pulverfömiger substance, granules or melt, aqueous solution or as a special formulation, mixed with the usual and known in the art auxiliaries, carriers and extenders or a combination of these agents. It is irrelevant whether the active ingredient in liquid form as z. As solution, emulsion or suspension or formulated in a solid form as dusts or dispersible powder. Wettable powders, emulsifiable concentrates and suspension concentrates usually, but not necessarily, contain surfactants, e.g. As a wetting, dispersing, emulsifying or suspending agent. The respective formulation methods correspond to the prior art and are known to the person skilled in the art.
Die erfindungsgemäßen Verbindungen, Zusammensetzungen und Düngemittel können beispielsweise bei der sowie zur Fertigation verwendet werden. Unter Fertigation versteht man die gezielte Zufuhr an Nährstoffen mit dem Bewässerungswasser, das z.B. durch Tropfbewässerung, Besprühen oder Berieseln ausgebracht werden kann. Die Pflanzen erhalten nur die zum optimalen Wachstum erforderliche Menge an Wasser, so dass kein Überschußwasser entsteht. Mangels einer vertikalen Wasserbewegung im Boden unterhalb der Durchwurzelungszone treten Nährstoffauswaschungsverluste praktisch nicht auf. Die Tropfbewässerung, Besprühung oder Berieselung mit Ureaseinhibitoren kann beispielsweise nach der Düngung erfolgen oder auch gemeinsam mit der Düngung. Natürlich besteht keine Beschränkung auf wässrige Lösungen oder sonstige Formulierungen. Beispielsweise können auch versprühbare Suspensionen feiner Teilchen verwendet werden. Insofern sei beispielhaft auf
Die vorliegende Erfindung soll nun anhand der folgenden Beispiele ohne Beschränkung und somit lediglich zur Veranschaulichung erläutert werden.The present invention will now be illustrated by the following examples without limitation and thus only by way of illustration.
In einem 100 ml Kolben mit Rückflusskühler und Trockenrohr werden 4,14 g (0,03 mol) 2-Nitroanilin und 6,25 g (0,03 mol) Phosphorpentachlorid in 50 ml Toluol suspendiert und unter Rühren 4 h zum Sieden erhitzt. Nach Abkühlen auf 80 °C werden langsam 1,38 g (0,03 mol) Ameisensäure zugegeben. Man lässt auf Raumtemperatur abkühlen, zieht das Lösungsmittel im Vakuum ab und wäscht den Rückstand mit Petrolether. Das zurückbleibende Öl wird ohne weitere Reinigung in 50 ml Chloroform aufgenommen und unter Feuchtigkeitsausschluss bei -50 bis -30 °C unter Rühren zu einer Lösung von ca. 30 ml flüssigem Ammoniak in 50 ml Chloroform getropft. Anschließend lässt man über Nacht bei Raumtemperatur das überschüssige Ammoniak abdampfen. Das ammoniumchloridhaltige Rohprodukt wird abgesaugt und zur Entfernung des Ammoniumchlorids entweder mit Diethylamin in Chloroform ausgekocht oder mit wenig Wasser gewaschen. Man erhält 3,6 g (55 %) N-(2-Nitrophenyl)phosphorsäuretriamid
Schmelzpunkt: ca. 200 °C (Zers.)
1H-NMR (DMSO-d6): δ [ppm] = 4,54 (s, 4 H, NH2); 6,96 (t, 1 H, CH); 7,60 (t, 1 H, CH); 7,93 (d, 1 H, CH); 8,11 (d, 1 H, CH): 8,34 (d, 1 H, NH)
13C-NMR (DMSO-d6): δ [ppm] = 118,8; 119,9 (d); 125,6; 133,9 (d); 135,6; 140,7 (d)
31P-NMR (DMSO-d6): δ [ppm] = 8,8In a 100 ml flask with reflux condenser and drying tube 4.14 g (0.03 mol) of 2-nitroaniline and 6.25 g (0.03 mol) of phosphorus pentachloride are suspended in 50 ml of toluene and heated with stirring for 4 h to boiling. After cooling to 80 ° C slowly 1.38 g (0.03 mol) of formic acid are added. The mixture is allowed to cool to room temperature, the solvent is removed in vacuo and the residue is washed with petroleum ether. The remaining oil is taken up without further purification in 50 ml of chloroform and added dropwise with exclusion of moisture at -50 to -30 ° C with stirring to a solution of about 30 ml of liquid ammonia in 50 ml of chloroform. Subsequently, the excess ammonia is allowed to evaporate overnight at room temperature. The ammonium chloride-containing crude product is filtered off with suction and, to remove the ammonium chloride, either boiled with diethylamine in chloroform or washed with a little water. This gives 3.6 g (55%) of N- (2-nitrophenyl) phosphoric triamide
Melting point: about 200 ° C (decomp.)
1 H-NMR (DMSO-d 6 ): δ [ppm] = 4.54 (s, 4H, NH 2 ); 6.96 (t, 1H, CH); 7.60 (t, 1H, CH); 7.93 (d, 1 H, CH); 8.11 (d, 1H, CH): 8.34 (d, 1H, NH)
13 C-NMR (DMSO-d 6 ): δ [ppm] = 118.8; 119.9 (d); 125.6; 133.9 (d); 135.6; 140.7 (d)
31 P-NMR (DMSO-d 6 ): δ [ppm] = 8.8
In einem 100 ml Kolben mit Rückflusskühler und Trockenrohr werden 14,3 g (0,1 mol) o-Toluidin-Hydrochlorid und 15,3 g (0,1 mol) Phosphorylchlorid in 50 ml Toluol suspendiert und unter Rühren 4 h zum Sieden erhitzt. Nach Abkühlen wird das Lösungsmittel von der entstandenen Lösung im Vakuum abgezogen und der Rückstand mit Petrolether gewaschen. Das zurückbleibende Öl wird ohne weitere Reinigung in 50 ml Chloroform aufgenommen und unter Feuchtigkeitsausschluss bei -50 bis -30 °C unter Rühren zu einer Lösung von ca. 70 ml flüssigem Ammoniak in 100 ml Chloroform getropft. Anschließend lässt man über Nacht bei Raumtemperatur das überschüssige Ammoniak abdampfen. Das ammoniumchloridhaltige Rohprodukt wird abgesaugt und zur Entfernung des Ammoniumchlorids entweder mit Diethylamin in Chloroform ausgekocht oder mit wenig Wasser gewaschen. Man erhält 9,1 g (49 %) N-(3-Methylphenyl)phosphorsäuretriamid.
Schmelzpunkt: 159 - 162°C
1H-NMR (DMSO-d6): δ [ppm] = 2,18 (s, 3 H, CH3); 3,9 (d, 4 H, NH2); 6,52 (d, 1 H, NH); 6,81 (d, 1 H, CH); 6,87-6,99 (m, 3H, CH)
13C-NMR (DMSO-d6) δ [ppm] = 21,3 (CH3); 114,3 (d); 117,5 (d); 119,4; 128,2 (d); 137,3; 143,4
31P-NMR (DMSO-d6): δ [ppm] = 11,6 (m)In a 100 ml flask with reflux condenser and drying tube 14.3 g (0.1 mol) of o-toluidine hydrochloride and 15.3 g (0.1 mol) of phosphoryl chloride are suspended in 50 ml of toluene and heated with stirring for 4 h to boiling , After cooling, the solvent is removed from the resulting solution in vacuo and the residue washed with petroleum ether. The remaining oil is added without further purification 50 ml of chloroform and added dropwise with exclusion of moisture at -50 to -30 ° C with stirring to a solution of about 70 ml of liquid ammonia in 100 ml of chloroform. Subsequently, the excess ammonia is allowed to evaporate overnight at room temperature. The ammonium chloride-containing crude product is filtered off with suction and, to remove the ammonium chloride, either boiled with diethylamine in chloroform or washed with a little water. This gives 9.1 g (49%) of N - (3-methylphenyl) phosphoric triamide.
Melting point: 159 - 162 ° C
1 H-NMR (DMSO-d 6 ): δ [ppm] = 2.18 (s, 3 H, CH 3 ); 3.9 (d, 4H, NH 2 ); 6.52 (d, 1H, NH); 6.81 (d, 1 H, CH); 6.87-6.99 (m, 3H, CH)
13 C-NMR (DMSO-d 6 ) δ [ppm] = 21.3 (CH 3 ); 114.3 (d); 117.5 (d); 119.4; 128.2 (d); 137.3; 143.4
31 P-NMR (DMSO-d 6 ): δ [ppm] = 11.6 (m)
In einem 200 ml Kolben mit Rückflusskühler und Trockenrohr werden 11,3 g (0,06 mol) 4-Methyl-2-nitroanilin-Hydrochlorid in 100 ml Phosphorylchlorid suspendiert und unter Rühren 4 h zum Sieden erhitzt. Anschließend verfährt man analog zu Beispiel 2. Man erhält 4,9 g (35 %) N-(4-Methyl-2-nitrophenyl)phosphorsäuretriamid.
Schmelzpunkt: > 180 °C (Zers.)
1H-NMR (DMSO-d6): δ [ppm] = 2,28 (s, 3 H, CH3); 4,50 (d, 4 H, NH2); 7,43 (d, 1 H, CH); 7,84 (d, 1 H, CH); 7,91 (s, 1 H, CH); 8,25 (d, 1 H, NH)
13C-NMR (DMSO-d6): δ [ppm] = 19,2 (CH3); 119,5; 124,3; 127,8; 133,2 (d); 136,5; 138,2 (d)
31P-NMR (DMSO-d6): δ [ppm] = 8,9In a 200 ml flask with reflux condenser and drying tube 11.3 g (0.06 mol) of 4-methyl-2-nitroaniline hydrochloride are suspended in 100 ml of phosphoryl chloride and heated with stirring for 4 h to boiling. The procedure is analogous to Example 2. 4.9 g (35%) of N- (4-methyl-2-nitrophenyl) phosphoric triamide are obtained.
Melting point:> 180 ° C (decomp.)
1 H-NMR (DMSO-d 6 ): δ [ppm] = 2.28 (s, 3 H, CH 3 ); 4.50 (d, 4H, NH 2 ); 7.43 (d, 1 H, CH); 7.84 (d, 1H, CH); 7.91 (s, 1H, CH); 8.25 (d, 1H, NH)
13 C-NMR (DMSO-d 6 ): δ [ppm] = 19.2 (CH 3 ); 119.5; 124.3; 127.8; 133.2 (d); 136.5; 138.2 (d)
31 P-NMR (DMSO-d 6 ): δ [ppm] = 8.9
30 g auf 40 % der maximalen Wasserkapazität eingestellter Boden werden mit 1 ml Harnstofflösung entsprechend 50 mg Harnstoff versetzt. Gleichzeitig erfolgt die Applikation des Wirkstoffes, vorzugsweise in der Harnstofflösung gelöst. Die Konzentrationsangaben für die einzelnen geprüften Wirkstoffe in der nachfolgenden Tabelle beziehen sich auf die im Test verwendete Menge an Carbamidstickstoff. Der Boden, auf dessen Oberfläche die Harnstofflösung (mit und ohne Wirkstoff) aufgebracht wird, befindet sich in einem luftdicht verschlossenen Gefäß, in das gleichzeitig eine Vorlage eingebracht wird, die den aus dem Harnstoff freigesetzte Ammoniak als Ammonium auffängt. Durch tägliches Überspülen der Vorlage und Analyse der enthaltenen NH4-N-Mengen wird die NH3-N-Freisetzung aus dem Harnstoff bestimmt.30 g of soil adjusted to 40% of the maximum water capacity are mixed with 1 ml of urea solution corresponding to 50 mg of urea. At the same time the application of the active ingredient, preferably dissolved in the urea solution. The concentration data for the individual tested active substances in the table below relate to the amount of carbamide nitrogen used in the test. The floor, on the surface of the urea solution (with and without active ingredient) is applied, located in an airtight container, in the same time an original is introduced, which captures the liberated from the urea ammonia as ammonium. By daily rinsing the template and analyzing the NH 4 -N levels contained, the NH 3 -N release from the urea is determined.
Aus der Summation der Ammonium-Mengen in der Vorlage wird die prozentuale Hemmung der Harnstoff-Hydrolyse in Abhängigkeit von der Zeit berechnet bzw. aus diesen Werten der t50-Wert rechnerisch ermittelt.From the summation of the ammonium amounts in the template, the percentage inhibition of the urea hydrolysis is calculated as a function of time or calculated from these values of the t 50 value.
Als t50-Wert wird der Zeitpunkt in Tagen nach Versuchsbeginn verstanden, zu dem die Hemmung der Harnstoff-Hydrolyse noch 50 % beträgt.The t 50 value is the time in days after the start of the experiment at which the inhibition of urea hydrolysis is still 50%.
Tabelle 1 gibt einen Überblick über die nach dieser Methode ermittelten Hemmdaten einiger ausgewählter erfindungsgemäßer Verbindungen.
%HS-N-bez.
(d)
b) nach 25 Tagen noch 70 % Hemmung
*Vergleichsbeispiel
% HS-N-mar.
(D)
b) 70% inhibition after 25 days
* Comparative Example
Claims (18)
- N-(2-nitrophenyl)phosphoric acid triamides with the general formula (I):
it being possible, if appropriate, to substitute the moieties R1-R4, themselves and independently of one another, for one or more of the aforementioned groups and by amino, alkylamino, dialkylamino, hydroxy, mercapto,
and salts, tautomers and metal complexes of compounds with the general formula (I) which have a urease-inhibiting effect. - The N-(2-nitrophenyl)phosphoric acid triamide according to Claim 1, in formula (I) X = O and R1 = R2 = R3 = R4 = H.
- A process for the production of the N-(2-nitrophenyl)phosphoric acid triamides according to either Claim 1 or 2, characterised in thata1) one converts 2-nitroanilines or the hydrochlorides of the latter with phosphoryl chloride POCl3) or thiphosphoryl chloride (PSCl3), if appropriate in the presence of an organic solvent and a tertiary base, at temperatures of 0 to 150°C, optionally in an inert gas atmosphere, in accordance with equation (1) into type (A) N-(2-nitrophenyl)phosphoric acid amide chlorides, it also alternatively being possible to obtain compounds (A) with X = S by sulphurisation of the corresponding oxygen derivatives,
- A composition, characterised in that it contains at least one N-(2-nitrophenyl)phosphoric acid triamide according to either of Claims 1 or 2 in a quantity sufficient to inhibit urease and optionally agriculturally and/or phsyiologically acceptable or compatible or desired carrier means, extenders or thinning agents, additives and optionally further active agents.
- The composition according to Claim 4, characterised in that as a further active agent at least one nitrification inhibitor is included in a quantity effective for nitrification inhibition.
- The composition according to Claim 5, characterised in that the nitrification inhibitor is selected from one or more of the following compounds:a) pyrazole derivatives with the general formula (IV), or salts or complex compounds of the latter:
andA means the moiety H
or the moiety
or the moiety
-CH2-B with B = (di)alkylamino,
or Cl andR12 = H orand the alkyl and aryl moieties listed can be substituted with themselves or with C1-C4-alkylsulfonyl, C1-C4-alkoxy, C1-C4-acyl, halogen, hydroxyl, trimethylsilyl, amino, nitro, sulfo, cyano, carbonyl, carboxyl or C1-C5-carboxylalkyl,
or the moiety - A fertiliser composition, characterised in that it contains at least one urea-based, mineral and/or organic fertiliser and at least one N-(2-nitrophenyl)phosphoric acid triamide according to either of Claims 1 or 2 and/or a composition according to any of Claims 4 to 6 or at least one N-(2-nitrophenyl)phosphoric acid triamide according to either of Claims 1 or 2 and at least one nitrification inhibitor defined in Claim 6 respectively in a quantity sufficient to inhibit urease or to inhibit nitrification.
- The fertiliser composition according to Claim 7, characterised in that at least one N-(2-nitrophenyl)phosphoric acid triamide according to either of Claims 1 or 2 is included in a quantity of 0.001 to 10 % by weight in relation to the weight of the urea-based fertiliser.
- The fertiliser composition according to Claim 7, characterised in that at least one of the nitrification inhibitors defined in Claim 6 is included in a quantity of 0.01 to 10 % by weight in relation to the weight of the urea-based fertiliser.
- Use of the N-(2-nitrophenyl)phosphoric acid triamides according to either of Claims 1 or 2 or of the compositions according to any of Claims 4 to 6 for the extra-corporeal regulation or inhibition of the urease-catalysed urea hydrolysis.
- Use of the N-(2-nitrophenyl)phosphoric acid triamides according to either of Claims 1 or 2 or of the compositions according to any of Claims 4 to 6 in order to reduce nitrogen losses when fertilising with fertilising urea or urea-based fertilisers.
- Use of the N-(2-nitrophenyl)phosphoric acid triamides according to any of Claims 1 or 2 or of the compositions according to any of Claims 4 to 6 in order to reduce the ammonia contamination from the manure or from the animal excrement in animal sheds.
- Use of N-(2-nitrophenyl)phosphoric acid triamides according to either of Claims 1 or 2 or of the compositions according to any of Claims 4 to 6 in order to avoid toxic effects when feeding feed urea within the framework of animal food.
- Use of N-(2-nitrophenyl)phosphoric acid triamides according to either of Claims 1 or 2 or of the aqueous solutions or liquid formulations of the latter in order to stabilise urea-based fertilisers already produced or still to be produced by downstream or upstream application.
- Use of the compositions according to any of Claims 4 to 6 for fertigation.
- Use of N-(2-nitrophenyl)phosphoric acid triamides according to any of Claims 1 or 2 or of the composition according to Claim 4 in order to produce a drug for the prophylaxis or therapy of problems or diseases which were induced or promoted directly or indirectly by urease activity.
- The use according to Claim 16, the problem or disease being selected from catheter incrustation, inflammatory and ulcerous gastric and intestinal diseases, urolithiasis, pyelonephritis, nephrolithiasis, ammonia encephalopathy, hepatic encephalopathy, hepatic coma, infections of the urinary passage and gastrointestinal infections.
- The use according to Claim 17, the gastrointestinal infection being caused by Helicobacter pylori.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102004035742A DE102004035742A1 (en) | 2004-07-23 | 2004-07-23 | N-phenylphosphoric triamides, processes for their preparation and their use as agents for regulating or inhibiting enzymatic urea hydrolysis |
| PCT/EP2005/001157 WO2006010389A1 (en) | 2004-07-23 | 2005-02-04 | N-phenylphosphoric acid triamides, method for the production thereof and their use as agents for regulating or inhibiting enzymatic urea hydrolysis |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| EP1771458A1 EP1771458A1 (en) | 2007-04-11 |
| EP1771458B1 EP1771458B1 (en) | 2009-08-05 |
| EP1771458B9 true EP1771458B9 (en) | 2011-02-02 |
Family
ID=34960210
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP05701353A Active EP1771458B9 (en) | 2004-07-23 | 2005-02-04 | N-phenylphosphoric acid triamides, method for the production thereof and their use as agents for regulating or inhibiting enzymatic urea hydrolysis |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US7855189B2 (en) |
| EP (1) | EP1771458B9 (en) |
| JP (1) | JP4954070B2 (en) |
| CN (1) | CN100588659C (en) |
| AT (1) | ATE438652T1 (en) |
| AU (1) | AU2005266693B2 (en) |
| BR (1) | BRPI0512103B8 (en) |
| CA (1) | CA2573543C (en) |
| DE (2) | DE102004035742A1 (en) |
| ES (1) | ES2332099T3 (en) |
| NZ (1) | NZ552812A (en) |
| PT (1) | PT1771458E (en) |
| RU (1) | RU2370498C2 (en) |
| UA (1) | UA89050C2 (en) |
| WO (1) | WO2006010389A1 (en) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7957356B2 (en) | 2002-05-13 | 2011-06-07 | Misomino Chi Acquisitions L.L.C. | Scalable media access control for multi-hop high bandwidth communications |
| EP1820788A1 (en) * | 2006-02-16 | 2007-08-22 | BASF Aktiengesellschaft | Preparations with improved urease-inhibiting properties and those preparations containing urea based fertilizers. |
| DE102007062614C5 (en) * | 2007-12-22 | 2019-03-14 | Eurochem Agro Gmbh | Mixture for the treatment of urea-containing fertilizers, uses of the mixture and urea-containing fertilizer containing the mixture |
| EP2107064A1 (en) * | 2008-04-02 | 2009-10-07 | Basf Se | Method for producing triamides from ammonia and amido-dichlorides |
| CZ302400B6 (en) * | 2008-10-20 | 2011-05-04 | Agra Group, A.S. | Process for preparing N-(hydrocarbyl)triamides of phosphoric or thiophosphoric acid |
| DE102009056566B4 (en) | 2009-12-03 | 2021-11-04 | Skw Stickstoffwerke Piesteritz Gmbh | Process for the preparation of phosphoric acid triamides in a one-pot reaction |
| US9440890B2 (en) * | 2010-04-30 | 2016-09-13 | Koch Agronomic Services, Llc | Reaction products and methods for making and using same |
| JP6126227B2 (en) | 2012-10-01 | 2017-05-10 | ギャリー デイヴィッド マクナイト | Improved liquid formulation of urease inhibitor for fertilizer |
| DE102013012500A1 (en) | 2013-07-26 | 2015-01-29 | Skw Stickstoffwerke Piesteritz Gmbh | Use of phosphoric acid amides as dry stress tolerance improvers |
| AU2014354854B2 (en) * | 2013-11-26 | 2018-08-30 | Gary David Mcknight | Nitrification inhibitors designed for urea and manure based fertilizers |
| WO2015086823A2 (en) | 2013-12-13 | 2015-06-18 | Eurochem Agro Gmbh | Fertilizer mixture containing nitrification inhibitor |
| WO2015161195A1 (en) | 2014-04-17 | 2015-10-22 | Mcknight Gary David | Compositions and methods comprising ntrification inhibitors containing a mixture of protic and aprotic solvent systems |
| WO2015104699A2 (en) * | 2014-04-17 | 2015-07-16 | Basf Se | Combination of novel nitrification inhibitors and fungicides as well as combination of (thio)phosphoric acid triamides and fungicides |
| WO2015104700A2 (en) * | 2014-04-17 | 2015-07-16 | Basf Se | Combination of novel nitrification inhibitors and insecticides and/or nematicides as well as combination of (thio)phosphoric acid triamides and insecticides and/or nematicides |
| US9968092B2 (en) | 2014-04-17 | 2018-05-15 | Basf Se | Combination of novel nitrification inhibitors and biopesticides as well as combination of (thio)phosphoric acid triamides and biopesticides |
| US10501383B2 (en) | 2014-10-31 | 2019-12-10 | Koch Agronomic Services, Llc | Nitrification inhibitor compositions and methods of making thereof |
| EP3763691A1 (en) | 2014-12-23 | 2021-01-13 | Basf Se | Compositions with improved urease-inhibiting effect comprising (thio)phosphoric acid triamide and further compounds such as amines and colorants |
| TR201815697T4 (en) | 2015-06-22 | 2018-11-21 | Eurochem Agro Gmbh | Mixture for the treatment of urea-containing fertilizers. |
| CN106348988B (en) * | 2015-07-13 | 2019-04-16 | 科氏农艺服务有限责任公司 | Highly concentrated phosphoric triamide or thiophosphoryl triamide preparation |
| DE102016111537A1 (en) | 2016-04-20 | 2017-10-26 | Skw Stickstoffwerke Piesteritz Gmbh | PROCESS FOR PREPARING N- (2-NITROPHENYL) PHOSPHORIC ACID DIAMIDE |
| CN106008223B (en) * | 2016-05-31 | 2018-08-31 | 江苏隆昌化工有限公司 | A kind of method of nitrofying aromatic hydrocarbon chloride |
| EP3330241A1 (en) * | 2016-12-01 | 2018-06-06 | YARA International ASA | Fertilizer particle |
| WO2018116046A1 (en) * | 2016-12-22 | 2018-06-28 | Basf Se | Mixture of aryl substituted (thio)phosphoric acid triamide urease inhibitors with phosphorus-containing urea fertilizers |
| DE102017201608A1 (en) | 2017-02-01 | 2018-08-02 | Eurochem Agro Gmbh | 3,4-dimethylpyrazole-containing mixture and its use |
| US20220396531A1 (en) * | 2017-06-28 | 2022-12-15 | Soilgenic Technologies, Llc | Liquid Formulations of Urease Inhibitors for Fertilizers |
| US11866383B1 (en) | 2018-04-04 | 2024-01-09 | Synsus Private Label Partners, Llc | Nitrification inhibiting compositions and their use in agricultural applications |
| DE102018208770A1 (en) | 2018-06-04 | 2019-12-05 | Eurochem Agro Gmbh | Emulsion for the treatment of urea-containing fertilizers |
| CN111808132A (en) * | 2019-04-11 | 2020-10-23 | 西南科技大学 | Method for continuously and rapidly preparing N-phenyl thiophosphoryl dichloride by using microreactor |
| CN112341295A (en) * | 2020-10-13 | 2021-02-09 | 范正红 | Method for treating pig farm excrement and additive |
| DE102021108187A1 (en) | 2021-03-31 | 2022-10-06 | Skw Stickstoffwerke Piesteritz Gmbh | Granulated pH neutral urea ammonium sulphate fertilizer with urease inhibitor |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4242325A (en) | 1979-07-06 | 1980-12-30 | Morton-Norwich Products, Inc. | Phosphorotriamides as urease inhibitors |
| EP0119494A1 (en) * | 1983-03-16 | 1984-09-26 | Allied Corporation | Urease inhibited urea based fertilizer compositions containing phosphorus compounds |
| US4517004A (en) * | 1983-06-08 | 1985-05-14 | Allied Corporation | Aryl phosphoric triamide and aryl phosphorodiamidate urease and nitrification inhibitors and urease and nitrification inhibited urea and reduced nitrogen based fertilizer compositions |
| US5562655A (en) | 1994-08-12 | 1996-10-08 | United States Surgical Corporation | Surgical apparatus having a universal handle for actuating various attachments |
| WO1996040856A1 (en) * | 1995-06-07 | 1996-12-19 | The Procter & Gamble Company | Toilet bowl cleaners containing urease inhibitors |
| US6017950A (en) * | 1997-08-05 | 2000-01-25 | Millennium Pharmaceuticals, Inc. | Methods for controlling gram negative bacteria in mammals |
-
2004
- 2004-07-23 DE DE102004035742A patent/DE102004035742A1/en not_active Withdrawn
-
2005
- 2005-02-04 RU RU2007106879/04A patent/RU2370498C2/en not_active IP Right Cessation
- 2005-02-04 AT AT05701353T patent/ATE438652T1/en not_active IP Right Cessation
- 2005-02-04 BR BRPI0512103A patent/BRPI0512103B8/en not_active IP Right Cessation
- 2005-02-04 EP EP05701353A patent/EP1771458B9/en active Active
- 2005-02-04 WO PCT/EP2005/001157 patent/WO2006010389A1/en active Application Filing
- 2005-02-04 CN CN200580024675A patent/CN100588659C/en active Active
- 2005-02-04 PT PT05701353T patent/PT1771458E/en unknown
- 2005-02-04 NZ NZ552812A patent/NZ552812A/en not_active IP Right Cessation
- 2005-02-04 AU AU2005266693A patent/AU2005266693B2/en not_active Ceased
- 2005-02-04 CA CA2573543A patent/CA2573543C/en not_active Expired - Fee Related
- 2005-02-04 US US11/658,157 patent/US7855189B2/en not_active Expired - Fee Related
- 2005-02-04 ES ES05701353T patent/ES2332099T3/en active Active
- 2005-02-04 JP JP2007521803A patent/JP4954070B2/en not_active Expired - Fee Related
- 2005-02-04 DE DE502005007855T patent/DE502005007855D1/en active Active
- 2005-04-02 UA UAA200701879A patent/UA89050C2/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| RU2370498C2 (en) | 2009-10-20 |
| DE102004035742A1 (en) | 2006-03-16 |
| DE502005007855D1 (en) | 2009-09-17 |
| RU2007106879A (en) | 2008-09-10 |
| ATE438652T1 (en) | 2009-08-15 |
| US7855189B2 (en) | 2010-12-21 |
| CA2573543A1 (en) | 2006-02-02 |
| CN1989144A (en) | 2007-06-27 |
| ES2332099T3 (en) | 2010-01-26 |
| JP2008507481A (en) | 2008-03-13 |
| CN100588659C (en) | 2010-02-10 |
| WO2006010389A1 (en) | 2006-02-02 |
| US20080070871A1 (en) | 2008-03-20 |
| AU2005266693B2 (en) | 2009-01-29 |
| NZ552812A (en) | 2009-04-30 |
| EP1771458A1 (en) | 2007-04-11 |
| BRPI0512103B8 (en) | 2021-05-25 |
| ES2332099T9 (en) | 2011-03-30 |
| AU2005266693A1 (en) | 2006-02-02 |
| BRPI0512103A (en) | 2008-02-06 |
| JP4954070B2 (en) | 2012-06-13 |
| CA2573543C (en) | 2013-04-09 |
| EP1771458B1 (en) | 2009-08-05 |
| PT1771458E (en) | 2009-11-06 |
| UA89050C2 (en) | 2009-12-25 |
| BRPI0512103B1 (en) | 2019-01-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1771458B9 (en) | N-phenylphosphoric acid triamides, method for the production thereof and their use as agents for regulating or inhibiting enzymatic urea hydrolysis | |
| EP3109223B1 (en) | Compound for the treatment of urea-comprising fertilizers | |
| EP1986981B1 (en) | Preparations with improved urease-inhibiting properties and those preparations containing urea based fertilizers. | |
| EP1183220B1 (en) | Agents for improving the n-utilization of mineral and/or organic fertilizers that contain urea | |
| EP1163245B1 (en) | (thio) phosphoryl triamides for regulating the enzymatic urea hydrolysis | |
| EP1399454B1 (en) | Heterocyclically substituted (thio)phosphoric triamides | |
| EP1282628B1 (en) | N-(2-pyrimidinyl)(thio)phosphoric triamides, method for producing the same, and the use thereof as agents for regulating or inhibiting enzymatic urea hydrolysis | |
| DE102006015362B4 (en) | N- (pyrazolyalkyl) (thio) phosphoric triamides, process for their preparation and their use as agents for regulating or inhibiting enzymatic urea hydrolysis and nitrification | |
| WO2005007636A1 (en) | 1,2,4- thiadiazol-5-thio compounds and the derivatives thereof, methods for the production thereof and use thereof as urease and nitrification inhibitors | |
| DE10317895A1 (en) | Use of 1,3,4-oxa- or thiadiazol-2-yl-(thio)phosphoric acid triamide derivatives, as urease inhibitors for preventing decomposition of urea in fertilizers or feedstuffs | |
| WO2005035509A1 (en) | 1h-azolyl-methyl-amides, method for the production thereof and use thereof as nitrification inhibitors | |
| EP1756125B1 (en) | 1,1,3,3,3-pentaamino-1-oxo/thio-1lambda5,3lambda5-diphosphaz-2-enes, method for producing them and their use as agents for regulating or inhibiting enzymatic hydrolysis of urea | |
| DE102014014266B3 (en) | Use of pyrazole compounds as dry stress tolerance improvers | |
| DE2543999A1 (en) | FERTILIZER FOR SUPPLYING PLANTS WITH IRON | |
| DE1695915C3 (en) | Method of preventing the nitrification of ammonium nitrogen | |
| DE102008020785B4 (en) | Use of simple derivatives of 5-amino-1,2,4-thiadiazole to inhibit or control nitrification | |
| DE10252382A1 (en) | Regulating or inhibiting enzyme-catalyzed urea hydrolysis, e.g. for preventing decomposition of urea in fertilizers or feedstuffs, using tetraamino-phosphonium salts | |
| DE1592688C3 (en) | Process for the preparation of a cyanate ion-free fertilizer with a content of at least about 95% biuret | |
| DE10216751A1 (en) | Non-toxic urease inhibitors comprising 1,1,1,3,3,3-hexaamino-diphosphazenium salts, useful e.g. for preventing loss of nitrogen from urea-based fertilizers or for reducing ammonia formation in animal stalls |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| 17P | Request for examination filed |
Effective date: 20070105 |
|
| AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU MC NL PL PT RO SE SI SK TR |
|
| DAX | Request for extension of the european patent (deleted) | ||
| 17Q | First examination report despatched |
Effective date: 20081016 |
|
| GRAP | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOSNIGR1 |
|
| GRAS | Grant fee paid |
Free format text: ORIGINAL CODE: EPIDOSNIGR3 |
|
| GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
| AK | Designated contracting states |
Kind code of ref document: B1 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU MC NL PL PT RO SE SI SK TR |
|
| REG | Reference to a national code |
Ref country code: GB Ref legal event code: FG4D Free format text: NOT ENGLISH |
|
| REG | Reference to a national code |
Ref country code: CH Ref legal event code: EP |
|
| REG | Reference to a national code |
Ref country code: IE Ref legal event code: FG4D |
|
| REF | Corresponds to: |
Ref document number: 502005007855 Country of ref document: DE Date of ref document: 20090917 Kind code of ref document: P |
|
| REG | Reference to a national code |
Ref country code: PT Ref legal event code: SC4A Free format text: AVAILABILITY OF NATIONAL TRANSLATION Effective date: 20091029 |
|
| REG | Reference to a national code |
Ref country code: GR Ref legal event code: EP Ref document number: 20090402735 Country of ref document: GR |
|
| LTIE | Lt: invalidation of european patent or patent extension |
Effective date: 20090805 |
|
| REG | Reference to a national code |
Ref country code: ES Ref legal event code: FG2A Ref document number: 2332099 Country of ref document: ES Kind code of ref document: T3 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: FI Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20090805 Ref country code: LT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20090805 Ref country code: IS Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20091205 Ref country code: SE Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20090805 |
|
| NLV1 | Nl: lapsed or annulled due to failure to fulfill the requirements of art. 29p and 29m of the patents act | ||
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: NL Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20090805 Ref country code: SI Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20090805 Ref country code: PL Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20090805 |
|
| REG | Reference to a national code |
Ref country code: IE Ref legal event code: FD4D |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: BG Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20091105 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: IE Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20090805 Ref country code: RO Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20090805 Ref country code: CZ Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20090805 Ref country code: DK Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20090805 Ref country code: EE Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20090805 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SK Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20090805 |
|
| PLBE | No opposition filed within time limit |
Free format text: ORIGINAL CODE: 0009261 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT |
|
| 26N | No opposition filed |
Effective date: 20100507 |
|
| BERE | Be: lapsed |
Owner name: SKW STICKSTOFFWERKE PIESTERITZ G.M.B.H. Effective date: 20100228 |
|
| REG | Reference to a national code |
Ref country code: CH Ref legal event code: PL |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LI Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20100228 Ref country code: CH Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20100228 Ref country code: MC Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20100301 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: BE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20100228 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: AT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20100204 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: CY Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20090805 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: HU Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20100206 Ref country code: LU Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20100204 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: TR Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20090805 |
|
| REG | Reference to a national code |
Ref country code: FR Ref legal event code: PLFP Year of fee payment: 12 |
|
| REG | Reference to a national code |
Ref country code: FR Ref legal event code: PLFP Year of fee payment: 13 |
|
| REG | Reference to a national code |
Ref country code: FR Ref legal event code: PLFP Year of fee payment: 14 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: GR Payment date: 20240226 Year of fee payment: 20 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: ES Payment date: 20240301 Year of fee payment: 20 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: DE Payment date: 20240226 Year of fee payment: 20 Ref country code: PT Payment date: 20240131 Year of fee payment: 20 Ref country code: GB Payment date: 20240221 Year of fee payment: 20 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: IT Payment date: 20240227 Year of fee payment: 20 Ref country code: FR Payment date: 20240227 Year of fee payment: 20 |